[{"date_updated":"2024-03-05T09:27:47Z","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"status":"public","license":"https://creativecommons.org/licenses/by/4.0/","publication_status":"epub_ahead","oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"05","abstract":[{"lang":"eng","text":"Poxviruses are among the largest double-stranded DNA viruses, with members such as variola virus, monkeypox virus and the vaccination strain vaccinia virus (VACV). Knowledge about the structural proteins that form the viral core has remained sparse. While major core proteins have been annotated via indirect experimental evidence, their structures have remained elusive and they could not be assigned to individual core features. Hence, which proteins constitute which layers of the core, such as the palisade layer and the inner core wall, has remained enigmatic. Here we show, using a multi-modal cryo-electron microscopy (cryo-EM) approach in combination with AlphaFold molecular modeling, that trimers formed by the cleavage product of VACV protein A10 are the key component of the palisade layer. This allows us to place previously obtained descriptions of protein interactions within the core wall into perspective and to provide a detailed model of poxvirus core architecture. Importantly, we show that interactions within A10 trimers are likely generalizable over members of orthopox- and parapoxviruses."}],"project":[{"call_identifier":"FWF","grant_number":"P31445","name":"Structural conservation and diversity in retroviral capsid","_id":"26736D6A-B435-11E9-9278-68D0E5697425"}],"citation":{"chicago":"Datler, Julia, Jesse Hansen, Andreas Thader, Alois Schlögl, Lukas W Bauer, Victor-Valentin Hodirnau, and Florian KM Schur. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41594-023-01201-6\">https://doi.org/10.1038/s41594-023-01201-6</a>.","ieee":"J. Datler <i>et al.</i>, “Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores,” <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature, 2024.","ista":"Datler J, Hansen J, Thader A, Schlögl A, Bauer LW, Hodirnau V-V, Schur FK. 2024. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. Nature Structural &#38; Molecular Biology.","apa":"Datler, J., Hansen, J., Thader, A., Schlögl, A., Bauer, L. W., Hodirnau, V.-V., &#38; Schur, F. K. (2024). Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-023-01201-6\">https://doi.org/10.1038/s41594-023-01201-6</a>","mla":"Datler, Julia, et al. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural &#38; Molecular Biology</i>, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1038/s41594-023-01201-6\">10.1038/s41594-023-01201-6</a>.","short":"J. Datler, J. Hansen, A. Thader, A. Schlögl, L.W. Bauer, V.-V. Hodirnau, F.K. Schur, Nature Structural &#38; Molecular Biology (2024).","ama":"Datler J, Hansen J, Thader A, et al. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. <i>Nature Structural &#38; Molecular Biology</i>. 2024. doi:<a href=\"https://doi.org/10.1038/s41594-023-01201-6\">10.1038/s41594-023-01201-6</a>"},"has_accepted_license":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41594-023-01201-6"}],"publication":"Nature Structural & Molecular Biology","related_material":{"link":[{"relation":"press_release","description":"News on ISTA Website","url":"https://ista.ac.at/en/news/down-to-the-core-of-poxviruses/"}]},"external_id":{"pmid":["38316877"]},"title":"Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores","language":[{"iso":"eng"}],"doi":"10.1038/s41594-023-01201-6","publisher":"Springer Nature","year":"2024","type":"journal_article","author":[{"id":"3B12E2E6-F248-11E8-B48F-1D18A9856A87","last_name":"Datler","orcid":"0000-0002-3616-8580","first_name":"Julia","full_name":"Datler, Julia"},{"last_name":"Hansen","id":"1063c618-6f9b-11ec-9123-f912fccded63","first_name":"Jesse","full_name":"Hansen, Jesse"},{"first_name":"Andreas","full_name":"Thader, Andreas","id":"3A18A7B8-F248-11E8-B48F-1D18A9856A87","last_name":"Thader"},{"full_name":"Schlögl, Alois","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","last_name":"Schlögl","orcid":"0000-0002-5621-8100"},{"first_name":"Lukas W","full_name":"Bauer, Lukas W","id":"0c894dcf-897b-11ed-a09c-8186353224b0","last_name":"Bauer"},{"id":"3661B498-F248-11E8-B48F-1D18A9856A87","last_name":"Hodirnau","first_name":"Victor-Valentin","full_name":"Hodirnau, Victor-Valentin"},{"orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","last_name":"Schur","full_name":"Schur, Florian KM","first_name":"Florian KM"}],"oa":1,"_id":"14979","date_published":"2024-02-05T00:00:00Z","date_created":"2024-02-12T09:59:45Z","pmid":1,"department":[{"_id":"FlSc"},{"_id":"ScienComp"},{"_id":"EM-Fac"}],"acknowledgement":"We thank A. Bergthaler (Research Center for Molecular Medicine of the Austrian Academy of Sciences) for providing VACV WR. We thank A. Nicholas and his team at the ISTA proteomics facility, and S. Elefante at the ISTA Scientific Computing facility for their support. We also thank F. Fäßler, D. Porley, T. Muthspiel and other members of the Schur group for support and helpful discussions. We also thank D. Castaño-Díez for support with Dynamo. We thank D. Farrell for his help optimizing the Rosetta protocol to refine the atomic model into the cryo-EM map with symmetry.\r\n\r\nF.K.M.S. acknowledges support from ISTA and EMBO. F.K.M.S. also received support from the Austrian Science Fund (FWF) grant P31445. This publication has been made possible in part by CZI grant DAF2021-234754 and grant https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (funder https://doi.org/10.13039/100014989) awarded to F.K.M.S.\r\n\r\nThis research was also supported by the Scientific Service Units (SSUs) of ISTA through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), and the Electron Microscopy Facility (EMF). We also acknowledge the use of COSMIC45 and Colabfold46.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"article_processing_charge":"Yes (in subscription journal)","keyword":["Molecular Biology","Structural Biology"],"month":"02","quality_controlled":"1","publication_identifier":{"eissn":["1545-9985"],"issn":["1545-9993"]},"article_type":"original"},{"intvolume":"         7","keyword":["Structural Biology"],"file_date_updated":"2023-08-16T09:36:28Z","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","acknowledgement":"The NMR platform in Grenoble is part of the Grenoble Instruct-ERIC center (ISBG; UAR 3518 CNRS-CEA-UGA-EMBL) within the Grenoble Partnership for Structural Biology (PSB), supported by FRISBI (ANR-10-INBS-0005-02) and GRAL, financed within the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003). This work was supported by the European Research Council (StG-2012-311318-ProtDyn2Function to P.S.) and used the platforms of the Grenoble Instruct Center (ISBG; UMS 3518 CNRS-CEA-UJF-EMBL) with support from FRISBI (ANR-10-INSB-05–02) and GRAL (ANR-10-LABX-49–01) within the Grenoble Partnership for Structural Biology (PSB). We would like to thank Sergei Izmailov for developing and maintaining the pyxmolpp2 library. N.R.S. acknowledges support from St. Petersburg State University in a form of the grant 92425251 and the access to the MRR, MCT and CAMR resource centers. P.S. thanks Malcolm Levitt for pointing out the fact that “tensor asymmetry” is better called “tensor biaxiality”.","department":[{"_id":"PaSc"}],"pmid":1,"date_created":"2023-01-12T11:55:38Z","article_number":"100079","article_type":"original","volume":7,"publication_identifier":{"issn":["2590-1524"]},"quality_controlled":"1","month":"01","type":"journal_article","year":"2023","publisher":"Elsevier","doi":"10.1016/j.yjsbx.2022.100079","language":[{"iso":"eng"}],"date_published":"2023-01-01T00:00:00Z","_id":"12114","oa":1,"author":[{"last_name":"Gauto","first_name":"Diego F.","full_name":"Gauto, Diego F."},{"last_name":"Lebedenko","first_name":"Olga O.","full_name":"Lebedenko, Olga O."},{"orcid":"0000-0002-6401-5151","id":"36336939-eb97-11eb-a6c2-c83f1214ca79","last_name":"Becker","first_name":"Lea Marie","full_name":"Becker, Lea Marie"},{"last_name":"Ayala","full_name":"Ayala, Isabel","first_name":"Isabel"},{"last_name":"Lichtenecker","first_name":"Roman","full_name":"Lichtenecker, Roman"},{"last_name":"Skrynnikov","full_name":"Skrynnikov, Nikolai R.","first_name":"Nikolai R."},{"first_name":"Paul","full_name":"Schanda, Paul","last_name":"Schanda","id":"7B541462-FAF6-11E9-A490-E8DFE5697425","orcid":"0000-0002-9350-7606"}],"has_accepted_license":"1","scopus_import":"1","citation":{"ieee":"D. F. Gauto <i>et al.</i>, “Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD,” <i>Journal of Structural Biology: X</i>, vol. 7. Elsevier, 2023.","chicago":"Gauto, Diego F., Olga O. Lebedenko, Lea Marie Becker, Isabel Ayala, Roman Lichtenecker, Nikolai R. Skrynnikov, and Paul Schanda. “Aromatic Ring Flips in Differently Packed Ubiquitin Protein Crystals from MAS NMR and MD.” <i>Journal of Structural Biology: X</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.yjsbx.2022.100079\">https://doi.org/10.1016/j.yjsbx.2022.100079</a>.","ama":"Gauto DF, Lebedenko OO, Becker LM, et al. Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD. <i>Journal of Structural Biology: X</i>. 2023;7. doi:<a href=\"https://doi.org/10.1016/j.yjsbx.2022.100079\">10.1016/j.yjsbx.2022.100079</a>","short":"D.F. Gauto, O.O. Lebedenko, L.M. Becker, I. Ayala, R. Lichtenecker, N.R. Skrynnikov, P. Schanda, Journal of Structural Biology: X 7 (2023).","ista":"Gauto DF, Lebedenko OO, Becker LM, Ayala I, Lichtenecker R, Skrynnikov NR, Schanda P. 2023. Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD. Journal of Structural Biology: X. 7, 100079.","mla":"Gauto, Diego F., et al. “Aromatic Ring Flips in Differently Packed Ubiquitin Protein Crystals from MAS NMR and MD.” <i>Journal of Structural Biology: X</i>, vol. 7, 100079, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.yjsbx.2022.100079\">10.1016/j.yjsbx.2022.100079</a>.","apa":"Gauto, D. F., Lebedenko, O. O., Becker, L. M., Ayala, I., Lichtenecker, R., Skrynnikov, N. R., &#38; Schanda, P. (2023). Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD. <i>Journal of Structural Biology: X</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.yjsbx.2022.100079\">https://doi.org/10.1016/j.yjsbx.2022.100079</a>"},"title":"Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD","file":[{"file_name":"2023_JourStrucBiologyX_Gauto.pdf","file_size":5132322,"checksum":"b4b1c10a31018aafe053b7d55a470e54","file_id":"14064","date_created":"2023-08-16T09:36:28Z","success":1,"date_updated":"2023-08-16T09:36:28Z","creator":"dernst","access_level":"open_access","content_type":"application/pdf","relation":"main_file"}],"external_id":{"pmid":["36578472"]},"publication":"Journal of Structural Biology: X","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","status":"public","date_updated":"2023-08-16T09:37:25Z","abstract":[{"text":"Probing the dynamics of aromatic side chains provides important insights into the behavior of a protein because flips of aromatic rings in a protein’s hydrophobic core report on breathing motion involving a large part of the protein. Inherently invisible to crystallography, aromatic motions have been primarily studied by solution NMR. The question how packing of proteins in crystals affects ring flips has, thus, remained largely unexplored. Here we apply magic-angle spinning NMR, advanced phenylalanine 1H-13C/2H isotope labeling and MD simulation to a protein in three different crystal packing environments to shed light onto possible impact of packing on ring flips. The flips of the two Phe residues in ubiquitin, both surface exposed, appear remarkably conserved in the different crystal forms, even though the intermolecular packing is quite different: Phe4 flips on a ca. 10–20 ns time scale, and Phe45 are broadened in all crystals, presumably due to µs motion. Our findings suggest that intramolecular influences are more important for ring flips than intermolecular (packing) effects.","lang":"eng"}],"day":"01","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"publication_status":"published","oa_version":"Published Version"},{"_id":"12163","oa":1,"author":[{"first_name":"Martin","full_name":"Loose, Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","last_name":"Loose","orcid":"0000-0001-7309-9724"},{"first_name":"Albert","full_name":"Auer, Albert","last_name":"Auer","id":"3018E8C2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3580-2906"},{"id":"D96FFDA0-A884-11E9-9968-DC26E6697425","last_name":"Brognara","full_name":"Brognara, Gabriel","first_name":"Gabriel"},{"full_name":"Budiman, Hanifatul R","first_name":"Hanifatul R","id":"55380f95-15b2-11ec-abd3-aff8e230696b","last_name":"Budiman"},{"full_name":"Kowalski, Lukasz M","first_name":"Lukasz M","id":"e3a512e2-4bbe-11eb-a68a-e3857a7844c2","last_name":"Kowalski"},{"last_name":"Matijevic","id":"83c17ce3-15b2-11ec-abd3-f486545870bd","full_name":"Matijevic, Ivana","first_name":"Ivana"}],"date_published":"2023-03-01T00:00:00Z","year":"2023","publisher":"Wiley","doi":"10.1002/1873-3468.14540","language":[{"iso":"eng"}],"type":"journal_article","publication_identifier":{"eissn":["1873-3468"],"issn":["0014-5793"]},"quality_controlled":"1","month":"03","volume":597,"article_type":"review","isi":1,"acknowledgement":"The authors acknowledge support from IST Austria and helpful comments from the anonymous reviewers that helped to improve this manuscript. We apologize to the authors of primary literature and outstanding research not cited here due to space restraints.","department":[{"_id":"MaLo"}],"pmid":1,"date_created":"2023-01-12T12:09:58Z","intvolume":"       597","keyword":["Cell Biology","Genetics","Molecular Biology","Biochemistry","Structural Biology","Biophysics"],"file_date_updated":"2023-08-16T08:31:04Z","ddc":["570"],"article_processing_charge":"Yes (via OA deal)","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"Small GTPases play essential roles in the organization of eukaryotic cells. In recent years, it has become clear that their intracellular functions result from intricate biochemical networks of the GTPase and their regulators that dynamically bind to a membrane surface. Due to the inherent complexities of their interactions, however, revealing the underlying mechanisms of action is often difficult to achieve from in vivo studies. This review summarizes in vitro reconstitution approaches developed to obtain a better mechanistic understanding of how small GTPase activities are regulated in space and time.","lang":"eng"}],"tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"day":"01","page":"762-777","publication_status":"published","oa_version":"Published Version","date_updated":"2023-08-16T08:32:29Z","status":"public","file":[{"file_name":"2023_FEBSLetters_Loose.pdf","file_size":3148143,"checksum":"7492244d3f9c5faa1347ef03f6e5bc84","file_id":"14063","date_created":"2023-08-16T08:31:04Z","success":1,"date_updated":"2023-08-16T08:31:04Z","creator":"dernst","access_level":"open_access","content_type":"application/pdf","relation":"main_file"}],"title":"In vitro reconstitution of small GTPase regulation","external_id":{"isi":["000891573000001"],"pmid":["36448231"]},"publication":"FEBS Letters","citation":{"chicago":"Loose, Martin, Albert Auer, Gabriel Brognara, Hanifatul R Budiman, Lukasz M Kowalski, and Ivana Matijevic. “In Vitro Reconstitution of Small GTPase Regulation.” <i>FEBS Letters</i>. Wiley, 2023. <a href=\"https://doi.org/10.1002/1873-3468.14540\">https://doi.org/10.1002/1873-3468.14540</a>.","ieee":"M. Loose, A. Auer, G. Brognara, H. R. Budiman, L. M. Kowalski, and I. Matijevic, “In vitro reconstitution of small GTPase regulation,” <i>FEBS Letters</i>, vol. 597, no. 6. Wiley, pp. 762–777, 2023.","ista":"Loose M, Auer A, Brognara G, Budiman HR, Kowalski LM, Matijevic I. 2023. In vitro reconstitution of small GTPase regulation. FEBS Letters. 597(6), 762–777.","short":"M. Loose, A. Auer, G. Brognara, H.R. Budiman, L.M. Kowalski, I. Matijevic, FEBS Letters 597 (2023) 762–777.","mla":"Loose, Martin, et al. “In Vitro Reconstitution of Small GTPase Regulation.” <i>FEBS Letters</i>, vol. 597, no. 6, Wiley, 2023, pp. 762–77, doi:<a href=\"https://doi.org/10.1002/1873-3468.14540\">10.1002/1873-3468.14540</a>.","apa":"Loose, M., Auer, A., Brognara, G., Budiman, H. R., Kowalski, L. M., &#38; Matijevic, I. (2023). In vitro reconstitution of small GTPase regulation. <i>FEBS Letters</i>. Wiley. <a href=\"https://doi.org/10.1002/1873-3468.14540\">https://doi.org/10.1002/1873-3468.14540</a>","ama":"Loose M, Auer A, Brognara G, Budiman HR, Kowalski LM, Matijevic I. In vitro reconstitution of small GTPase regulation. <i>FEBS Letters</i>. 2023;597(6):762-777. doi:<a href=\"https://doi.org/10.1002/1873-3468.14540\">10.1002/1873-3468.14540</a>"},"has_accepted_license":"1","scopus_import":"1","issue":"6"},{"title":"Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography","file":[{"date_updated":"2024-02-08T23:30:04Z","file_id":"12527","date_created":"2023-02-07T13:07:38Z","checksum":"069d87f025e0799bf9e3c375664264f2","file_size":23082464,"file_name":"PhDThesis_BettinaZens_2023_final.pdf","relation":"main_file","content_type":"application/pdf","access_level":"open_access","embargo":"2024-02-07","creator":"bzens"},{"file_name":"PhDThesis_BettinaZens_2023_final.docx","file_size":106169509,"checksum":"8c66ed203495d6e078ed1002a866520c","file_id":"12528","date_created":"2023-02-07T13:09:05Z","date_updated":"2024-02-08T23:30:04Z","embargo_to":"open_access","creator":"bzens","access_level":"closed","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file"}],"related_material":{"record":[{"relation":"part_of_dissertation","id":"8586","status":"public"}]},"has_accepted_license":"1","alternative_title":["ISTA Thesis"],"citation":{"ieee":"B. Zens, “Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography,” Institute of Science and Technology Austria, 2023.","chicago":"Zens, Bettina. “Ultrastructural Characterization of Natively Preserved Extracellular Matrix by Cryo-Electron Tomography.” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/at:ista:12491\">https://doi.org/10.15479/at:ista:12491</a>.","ama":"Zens B. Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography. 2023. doi:<a href=\"https://doi.org/10.15479/at:ista:12491\">10.15479/at:ista:12491</a>","apa":"Zens, B. (2023). <i>Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12491\">https://doi.org/10.15479/at:ista:12491</a>","mla":"Zens, Bettina. <i>Ultrastructural Characterization of Natively Preserved Extracellular Matrix by Cryo-Electron Tomography</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/at:ista:12491\">10.15479/at:ista:12491</a>.","short":"B. Zens, Ultrastructural Characterization of Natively Preserved Extracellular Matrix by Cryo-Electron Tomography, Institute of Science and Technology Austria, 2023.","ista":"Zens B. 2023. Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography. Institute of Science and Technology Austria."},"project":[{"_id":"eba3b5f6-77a9-11ec-83b8-cf0905748aa3","name":"Integrated visual proteomics of reciprocal cell-extracellular matrix interactions"},{"name":"NÖ-Fonds Preis für die Jungforscherin des Jahres am IST Austria","_id":"059B463C-7A3F-11EA-A408-12923DDC885E"}],"day":"02","page":"187","publication_status":"published","oa_version":"Published Version","abstract":[{"lang":"eng","text":"The extracellular matrix (ECM) is a hydrated and complex three-dimensional network consisting of proteins, polysaccharides, and water. It provides structural scaffolding for the cells embedded within it and is essential in regulating numerous physiological processes, including cell migration and proliferation, wound healing, and stem cell fate. \r\nDespite extensive study, detailed structural knowledge of ECM components in physiologically relevant conditions is still rudimentary. This is due to methodological limitations in specimen preparation protocols which are incompatible with keeping large samples, such as the ECM, in their native state for subsequent imaging. Conventional electron microscopy (EM) techniques rely on fixation, dehydration, contrasting, and sectioning. This results in the alteration of a highly hydrated environment and the potential introduction of artifacts. Other structural biology techniques, such as nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, allow high-resolution analysis of protein structures but only work on homogenous and purified samples, hence lacking contextual information. Currently, no approach exists for the ultrastructural and structural study of extracellular components under native conditions in a physiological, 3D environment. \r\nIn this thesis, I have developed a workflow that allows for the ultrastructural analysis of the ECM in near-native conditions at molecular resolution. The developments I introduced include implementing a novel specimen preparation workflow for cell-derived matrices (CDMs) to render them compatible with ion-beam milling and subsequent high-resolution cryo-electron tomography (ET). \r\nTo this end, I have established protocols to generate CDMs grown over several weeks on EM grids that are compatible with downstream cryo-EM sample preparation and imaging techniques. Characterization of these ECMs confirmed that they contain essential ECM components such as collagen I, collagen VI, and fibronectin I in high abundance and hence represent a bona fide biologically-relevant sample. I successfully optimized vitrification of these specimens by testing various vitrification techniques and cryoprotectants. \r\nIn order to obtain high-resolution molecular insights into the ultrastructure and organization of CDMs, I established cryo-focused ion beam scanning electron microscopy (FIBSEM) on these challenging and complex specimens. I explored different approaches for the creation of thin cryo-lamellae by FIB milling and succeeded in optimizing the cryo-lift-out technique, resulting in high-quality lamellae of approximately 200 nm thickness. \r\nHigh-resolution Cryo-ET of these lamellae revealed for the first time the architecture of native CDM in the context of matrix-secreting cells. This allowed for the in situ visualization of fibrillar matrix proteins such as collagen, laying the foundation for future structural and ultrastructural characterization of these proteins in their near-native environment. \r\nIn summary, in this thesis, I present a novel workflow that combines state-of-the-art cryo-EM specimen preparation and imaging technologies to permit characterization of the ECM, an important tissue component in higher organisms. This innovative and highly versatile workflow will enable addressing far-reaching questions on ECM architecture, composition, and reciprocal ECM-cell interactions."}],"degree_awarded":"PhD","status":"public","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"Bio"}],"date_updated":"2024-02-08T23:30:05Z","supervisor":[{"orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","last_name":"Schur","first_name":"Florian KM","full_name":"Schur, Florian KM"}],"month":"02","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-027-5"]},"file_date_updated":"2024-02-08T23:30:04Z","article_processing_charge":"No","ddc":["570"],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","keyword":["cryo-EM","cryo-ET","FIB milling","method development","FIBSEM","extracellular matrix","ECM","cell-derived matrices","CDMs","cell culture","high pressure freezing","HPF","structural biology","tomography","collagen"],"date_created":"2023-02-02T14:50:20Z","department":[{"_id":"GradSch"},{"_id":"FlSc"}],"date_published":"2023-02-02T00:00:00Z","author":[{"last_name":"Zens","id":"45FD126C-F248-11E8-B48F-1D18A9856A87","first_name":"Bettina","full_name":"Zens, Bettina"}],"_id":"12491","oa":1,"type":"dissertation","doi":"10.15479/at:ista:12491","language":[{"iso":"eng"}],"year":"2023","publisher":"Institute of Science and Technology Austria"},{"status":"public","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"EM-Fac"}],"date_updated":"2023-08-03T06:25:23Z","abstract":[{"lang":"eng","text":"The potential of energy filtering and direct electron detection for cryo-electron microscopy (cryo-EM) has been well documented. Here, we assess the performance of recently introduced hardware for cryo-electron tomography (cryo-ET) and subtomogram averaging (STA), an increasingly popular structural determination method for complex 3D specimens. We acquired cryo-ET datasets of EIAV virus-like particles (VLPs) on two contemporary cryo-EM systems equipped with different energy filters and direct electron detectors (DED), specifically a Krios G4, equipped with a cold field emission gun (CFEG), Thermo Fisher Scientific Selectris X energy filter, and a Falcon 4 DED; and a Krios G3i, with a Schottky field emission gun (XFEG), a Gatan Bioquantum energy filter, and a K3 DED. We performed constrained cross-correlation-based STA on equally sized datasets acquired on the respective systems. The resulting EIAV CA hexamer reconstructions show that both systems perform comparably in the 4–6 Å resolution range based on Fourier-Shell correlation (FSC). In addition, by employing a recently introduced multiparticle refinement approach, we obtained a reconstruction of the EIAV CA hexamer at 2.9 Å. Our results demonstrate the potential of the new generation of energy filters and DEDs for STA, and the effects of using different processing pipelines on their STA outcomes."}],"day":"01","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication_status":"published","oa_version":"Published Version","has_accepted_license":"1","scopus_import":"1","issue":"2","citation":{"chicago":"Obr, Martin, Wim J.H. Hagen, Robert A. Dick, Lingbo Yu, Abhay Kotecha, and Florian KM Schur. “Exploring High-Resolution Cryo-ET and Subtomogram Averaging Capabilities of Contemporary DEDs.” <i>Journal of Structural Biology</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.jsb.2022.107852\">https://doi.org/10.1016/j.jsb.2022.107852</a>.","ieee":"M. Obr, W. J. H. Hagen, R. A. Dick, L. Yu, A. Kotecha, and F. K. Schur, “Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs,” <i>Journal of Structural Biology</i>, vol. 214, no. 2. Elsevier, 2022.","ista":"Obr M, Hagen WJH, Dick RA, Yu L, Kotecha A, Schur FK. 2022. Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs. Journal of Structural Biology. 214(2), 107852.","mla":"Obr, Martin, et al. “Exploring High-Resolution Cryo-ET and Subtomogram Averaging Capabilities of Contemporary DEDs.” <i>Journal of Structural Biology</i>, vol. 214, no. 2, 107852, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.jsb.2022.107852\">10.1016/j.jsb.2022.107852</a>.","short":"M. Obr, W.J.H. Hagen, R.A. Dick, L. Yu, A. Kotecha, F.K. Schur, Journal of Structural Biology 214 (2022).","apa":"Obr, M., Hagen, W. J. H., Dick, R. A., Yu, L., Kotecha, A., &#38; Schur, F. K. (2022). Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs. <i>Journal of Structural Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jsb.2022.107852\">https://doi.org/10.1016/j.jsb.2022.107852</a>","ama":"Obr M, Hagen WJH, Dick RA, Yu L, Kotecha A, Schur FK. Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs. <i>Journal of Structural Biology</i>. 2022;214(2). doi:<a href=\"https://doi.org/10.1016/j.jsb.2022.107852\">10.1016/j.jsb.2022.107852</a>"},"project":[{"name":"Structural conservation and diversity in retroviral capsid","_id":"26736D6A-B435-11E9-9278-68D0E5697425","grant_number":"P31445","call_identifier":"FWF"}],"file":[{"file_size":7080863,"file_name":"2022_JourStructuralBiology_Obr.pdf","date_updated":"2022-08-02T11:07:58Z","success":1,"date_created":"2022-08-02T11:07:58Z","file_id":"11722","checksum":"0b1eb53447aae8e95ae4c12d193b0b00","creator":"dernst","relation":"main_file","content_type":"application/pdf","access_level":"open_access"}],"title":"Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs","external_id":{"pmid":["35351542"],"isi":["000790733600001"]},"publication":"Journal of Structural Biology","type":"journal_article","year":"2022","publisher":"Elsevier","doi":"10.1016/j.jsb.2022.107852","language":[{"iso":"eng"}],"date_published":"2022-06-01T00:00:00Z","_id":"11155","oa":1,"author":[{"first_name":"Martin","full_name":"Obr, Martin","last_name":"Obr","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hagen","full_name":"Hagen, Wim J.H.","first_name":"Wim J.H."},{"last_name":"Dick","first_name":"Robert A.","full_name":"Dick, Robert A."},{"last_name":"Yu","full_name":"Yu, Lingbo","first_name":"Lingbo"},{"full_name":"Kotecha, Abhay","first_name":"Abhay","last_name":"Kotecha"},{"orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","last_name":"Schur","first_name":"Florian KM","full_name":"Schur, Florian KM"}],"intvolume":"       214","keyword":["Structural Biology"],"file_date_updated":"2022-08-02T11:07:58Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"Yes (via OA deal)","ddc":["570"],"acknowledgement":"This work was funded by the Austrian Science Fund (FWF) grant P31445 to F.K.M.S and the National Institute of Allergy and Infectious Diseases under awards R01AI147890 to R.A.D. This research was also supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), and the Electron Microscopy Facility (EMF). We thank Dustin Morado for providing the software SubTOM for data processing. We also thank William Wan for critical reading of the manuscript and valuable feedback.","department":[{"_id":"FlSc"}],"pmid":1,"date_created":"2022-04-15T07:10:26Z","article_number":"107852","volume":214,"article_type":"original","isi":1,"publication_identifier":{"issn":["1047-8477"]},"quality_controlled":"1","month":"06"},{"status":"public","date_updated":"2023-08-03T06:31:06Z","publication_status":"published","oa_version":"Published Version","day":"01","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"abstract":[{"lang":"eng","text":"Complex I is one of the major respiratory complexes, conserved from bacteria to mammals. It oxidises NADH, reduces quinone and pumps protons across the membrane, thus playing a central role in the oxidative energy metabolism. In this review we discuss our current state of understanding the structure of complex I from various species of mammals, plants, fungi, and bacteria, as well as of several complex I-related proteins. By comparing the structural evidence from these systems in different redox states and data from mutagenesis and molecular simulations, we formulate the mechanisms of electron transfer and proton pumping and explain how they are conformationally and electrostatically coupled. Finally, we discuss the structural basis of the deactivation phenomenon in mammalian complex I."}],"scopus_import":"1","has_accepted_license":"1","citation":{"ama":"Kampjut D, Sazanov LA. Structure of respiratory complex I – An emerging blueprint for the mechanism. <i>Current Opinion in Structural Biology</i>. 2022;74. doi:<a href=\"https://doi.org/10.1016/j.sbi.2022.102350\">10.1016/j.sbi.2022.102350</a>","apa":"Kampjut, D., &#38; Sazanov, L. A. (2022). Structure of respiratory complex I – An emerging blueprint for the mechanism. <i>Current Opinion in Structural Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.sbi.2022.102350\">https://doi.org/10.1016/j.sbi.2022.102350</a>","mla":"Kampjut, Domen, and Leonid A. Sazanov. “Structure of Respiratory Complex I – An Emerging Blueprint for the Mechanism.” <i>Current Opinion in Structural Biology</i>, vol. 74, 102350, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.sbi.2022.102350\">10.1016/j.sbi.2022.102350</a>.","ista":"Kampjut D, Sazanov LA. 2022. Structure of respiratory complex I – An emerging blueprint for the mechanism. Current Opinion in Structural Biology. 74, 102350.","short":"D. Kampjut, L.A. Sazanov, Current Opinion in Structural Biology 74 (2022).","ieee":"D. Kampjut and L. A. Sazanov, “Structure of respiratory complex I – An emerging blueprint for the mechanism,” <i>Current Opinion in Structural Biology</i>, vol. 74. Elsevier, 2022.","chicago":"Kampjut, Domen, and Leonid A Sazanov. “Structure of Respiratory Complex I – An Emerging Blueprint for the Mechanism.” <i>Current Opinion in Structural Biology</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.sbi.2022.102350\">https://doi.org/10.1016/j.sbi.2022.102350</a>."},"publication":"Current Opinion in Structural Biology","external_id":{"isi":["000829029500020"],"pmid":["35316665"]},"file":[{"creator":"dernst","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_name":"2022_CurrentOpStructBiology_Kampjut.pdf","file_size":815607,"date_created":"2022-08-05T05:56:03Z","checksum":"72bdde48853643a32d42b75f54965c44","file_id":"11725","date_updated":"2022-08-05T05:56:03Z","success":1}],"title":"Structure of respiratory complex I – An emerging blueprint for the mechanism","type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1016/j.sbi.2022.102350","publisher":"Elsevier","year":"2022","date_published":"2022-06-01T00:00:00Z","author":[{"first_name":"Domen","full_name":"Kampjut, Domen","id":"37233050-F248-11E8-B48F-1D18A9856A87","last_name":"Kampjut"},{"full_name":"Sazanov, Leonid A","first_name":"Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989"}],"oa":1,"_id":"11167","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"Yes (via OA deal)","ddc":["570"],"file_date_updated":"2022-08-05T05:56:03Z","keyword":["Molecular Biology","Structural Biology"],"intvolume":"        74","date_created":"2022-04-15T09:32:35Z","article_number":"102350","pmid":1,"department":[{"_id":"LeSa"}],"isi":1,"article_type":"original","volume":74,"month":"06","quality_controlled":"1","publication_identifier":{"issn":["0959-440X"]}},{"citation":{"ieee":"C. Gerle <i>et al.</i>, “Structures of multisubunit membrane complexes with the CRYO ARM 200,” <i>Microscopy</i>, vol. 71, no. 5. Oxford University Press, pp. 249–261, 2022.","chicago":"Gerle, Christoph, Jun-ichi Kishikawa, Tomoko Yamaguchi, Atsuko Nakanishi, Mehmet Orkun Çoruh, Fumiaki Makino, Tomoko Miyata, et al. “Structures of Multisubunit Membrane Complexes with the CRYO ARM 200.” <i>Microscopy</i>. Oxford University Press, 2022. <a href=\"https://doi.org/10.1093/jmicro/dfac037\">https://doi.org/10.1093/jmicro/dfac037</a>.","ama":"Gerle C, Kishikawa J, Yamaguchi T, et al. Structures of multisubunit membrane complexes with the CRYO ARM 200. <i>Microscopy</i>. 2022;71(5):249-261. doi:<a href=\"https://doi.org/10.1093/jmicro/dfac037\">10.1093/jmicro/dfac037</a>","ista":"Gerle C, Kishikawa J, Yamaguchi T, Nakanishi A, Çoruh MO, Makino F, Miyata T, Kawamoto A, Yokoyama K, Namba K, Kurisu G, Kato T. 2022. Structures of multisubunit membrane complexes with the CRYO ARM 200. Microscopy. 71(5), 249–261.","short":"C. Gerle, J. Kishikawa, T. Yamaguchi, A. Nakanishi, M.O. Çoruh, F. Makino, T. Miyata, A. Kawamoto, K. Yokoyama, K. Namba, G. Kurisu, T. Kato, Microscopy 71 (2022) 249–261.","mla":"Gerle, Christoph, et al. “Structures of Multisubunit Membrane Complexes with the CRYO ARM 200.” <i>Microscopy</i>, vol. 71, no. 5, Oxford University Press, 2022, pp. 249–61, doi:<a href=\"https://doi.org/10.1093/jmicro/dfac037\">10.1093/jmicro/dfac037</a>.","apa":"Gerle, C., Kishikawa, J., Yamaguchi, T., Nakanishi, A., Çoruh, M. O., Makino, F., … Kato, T. (2022). Structures of multisubunit membrane complexes with the CRYO ARM 200. <i>Microscopy</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/jmicro/dfac037\">https://doi.org/10.1093/jmicro/dfac037</a>"},"has_accepted_license":"1","scopus_import":"1","issue":"5","file":[{"relation":"main_file","content_type":"application/pdf","access_level":"open_access","creator":"dernst","date_updated":"2023-02-03T08:34:48Z","success":1,"checksum":"23b51c163636bf9313f7f0818312e67e","date_created":"2023-02-03T08:34:48Z","file_id":"12498","file_size":7812696,"file_name":"2022_Microscopy_Gerle.pdf"}],"title":"Structures of multisubunit membrane complexes with the CRYO ARM 200","external_id":{"pmid":["35861182"],"isi":["000837950900001"]},"publication":"Microscopy","date_updated":"2023-08-03T12:13:37Z","status":"public","abstract":[{"lang":"eng","text":"Progress in structural membrane biology has been significantly accelerated by the ongoing 'Resolution Revolution' in cryo electron microscopy (cryo-EM). In particular, structure determination by single particle analysis has evolved into the most powerful method for atomic model building of multisubunit membrane protein complexes. This has created an ever increasing demand in cryo-EM machine time, which to satisfy is in need of new and affordable cryo electron microscopes. Here, we review our experience in using the JEOL CRYO ARM 200 prototype for the structure determination by single particle analysis of three different multisubunit membrane complexes: the Thermus thermophilus V-type ATPase VO complex, the Thermosynechococcus elongatus photosystem I monomer and the flagellar motor LP-ring from Salmonella enterica."}],"day":"01","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"oa_version":"Published Version","publication_status":"published","page":"249-261","department":[{"_id":"LeSa"}],"acknowledgement":"Cyclic Innovation for Clinical Empowerment (JP17pc0101020 from Japan Agency for Medical Research and Development (AMED) to K.N. and G.K.); Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research) from AMED (JP20am0101117 to K.N., JP16K07266 to Atsunori Oshima and C.G., JP22ama121001j0001 to Masaki Yamamoto, G.K., T.K. and C.G.); a JSPS KAHKENHI\r\ngrant (20K06514 to J.K.) and a Grant-in-aid for JSPS fellows (20J00162 to A.N.).\r\nWe are grateful for initiation and scientific support from Matthias Rogner, Marc M. Nowaczyk, Anna Frank and ̈Yuko Misumi for the PSI monomer project and also would like to thank Hideki Shigematsu for critical reading of the manuscript. And we are indebted to the two anonymous reviewers who helped us to improve our manuscript.","pmid":1,"date_created":"2022-07-25T10:04:58Z","intvolume":"        71","keyword":["Radiology","Nuclear Medicine and imaging","Instrumentation","Structural Biology"],"file_date_updated":"2023-02-03T08:34:48Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","ddc":["570"],"publication_identifier":{"eissn":["2050-5701"],"issn":["2050-5698"]},"quality_controlled":"1","month":"10","volume":71,"article_type":"original","isi":1,"year":"2022","publisher":"Oxford University Press","doi":"10.1093/jmicro/dfac037","language":[{"iso":"eng"}],"type":"journal_article","_id":"11648","oa":1,"author":[{"first_name":"Christoph","full_name":"Gerle, Christoph","last_name":"Gerle"},{"last_name":"Kishikawa","first_name":"Jun-ichi","full_name":"Kishikawa, Jun-ichi"},{"last_name":"Yamaguchi","full_name":"Yamaguchi, Tomoko","first_name":"Tomoko"},{"last_name":"Nakanishi","full_name":"Nakanishi, Atsuko","first_name":"Atsuko"},{"orcid":"0000-0002-3219-2022","id":"d25163e5-8d53-11eb-a251-e6dd8ea1b8ef","last_name":"Çoruh","first_name":"Mehmet Orkun","full_name":"Çoruh, Mehmet Orkun"},{"last_name":"Makino","first_name":"Fumiaki","full_name":"Makino, Fumiaki"},{"first_name":"Tomoko","full_name":"Miyata, Tomoko","last_name":"Miyata"},{"last_name":"Kawamoto","first_name":"Akihiro","full_name":"Kawamoto, Akihiro"},{"first_name":"Ken","full_name":"Yokoyama, Ken","last_name":"Yokoyama"},{"last_name":"Namba","full_name":"Namba, Keiichi","first_name":"Keiichi"},{"last_name":"Kurisu","first_name":"Genji","full_name":"Kurisu, Genji"},{"first_name":"Takayuki","full_name":"Kato, Takayuki","last_name":"Kato"}],"date_published":"2022-10-01T00:00:00Z"},{"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"file_date_updated":"2023-01-30T10:00:04Z","keyword":["Molecular Biology","Structural Biology"],"intvolume":"        29","date_created":"2023-01-16T09:59:06Z","pmid":1,"department":[{"_id":"EM-Fac"}],"acknowledgement":"We thank M. Fromont-Racine, A. Johnson, J. Woolford, S. Rospert, J. P. G. Ballesta and\r\nE. Hurt for supplying antibodies. The work was supported by Boehringer Ingelheim (to\r\nD. H.), the Austrian Science Foundation FWF (grants 32536 and 32977 to H. B.), the\r\nUK Medical Research Council (MR/T012412/1 to A. J. W.) and the German Research\r\nFoundation (Emmy Noether Programme STE 2517/1-1 and STE 2517/5-1 to F.S.). We\r\nthank Norberto Escudero-Urquijo, Pablo Castro-Hartmann and K. Dent, Cambridge\r\nInstitute for Medical Research, for their help in cryo-EM during early phases of this\r\nproject. This research was supported by the Scientific Service Units of IST Austria through\r\nresources provided by the Electron Microscopy Facility. We thank S. Keller, Institute of\r\nMolecular Biosciences (Biophysics), University Graz for support with the quantification of\r\nthe SPR particle release assay. We thank I. Schaffner, University of Natural Resources and\r\nLife Sciences, Vienna for her help in early stages of the SPR experiments.","isi":1,"volume":29,"article_type":"original","month":"09","quality_controlled":"1","publication_identifier":{"issn":["1545-9993"],"eissn":["1545-9985"]},"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1038/s41594-022-00832-5","publisher":"Springer Nature","year":"2022","date_published":"2022-09-12T00:00:00Z","author":[{"first_name":"Michael","full_name":"Prattes, Michael","last_name":"Prattes"},{"full_name":"Grishkovskaya, Irina","first_name":"Irina","last_name":"Grishkovskaya"},{"full_name":"Hodirnau, Victor-Valentin","first_name":"Victor-Valentin","id":"3661B498-F248-11E8-B48F-1D18A9856A87","last_name":"Hodirnau"},{"full_name":"Hetzmannseder, Christina","first_name":"Christina","last_name":"Hetzmannseder"},{"last_name":"Zisser","full_name":"Zisser, Gertrude","first_name":"Gertrude"},{"last_name":"Sailer","first_name":"Carolin","full_name":"Sailer, Carolin"},{"last_name":"Kargas","first_name":"Vasileios","full_name":"Kargas, Vasileios"},{"first_name":"Mathias","full_name":"Loibl, Mathias","last_name":"Loibl"},{"last_name":"Gerhalter","full_name":"Gerhalter, Magdalena","first_name":"Magdalena"},{"last_name":"Kofler","first_name":"Lisa","full_name":"Kofler, Lisa"},{"full_name":"Warren, Alan J.","first_name":"Alan J.","last_name":"Warren"},{"first_name":"Florian","full_name":"Stengel, Florian","last_name":"Stengel"},{"last_name":"Haselbach","first_name":"David","full_name":"Haselbach, David"},{"full_name":"Bergler, Helmut","first_name":"Helmut","last_name":"Bergler"}],"oa":1,"_id":"12262","issue":"9","scopus_import":"1","has_accepted_license":"1","citation":{"ista":"Prattes M, Grishkovskaya I, Hodirnau V-V, Hetzmannseder C, Zisser G, Sailer C, Kargas V, Loibl M, Gerhalter M, Kofler L, Warren AJ, Stengel F, Haselbach D, Bergler H. 2022. Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1. Nature Structural &#38; Molecular Biology. 29(9), 942–953.","mla":"Prattes, Michael, et al. “Visualizing Maturation Factor Extraction from the Nascent Ribosome by the AAA-ATPase Drg1.” <i>Nature Structural &#38; Molecular Biology</i>, vol. 29, no. 9, Springer Nature, 2022, pp. 942–53, doi:<a href=\"https://doi.org/10.1038/s41594-022-00832-5\">10.1038/s41594-022-00832-5</a>.","short":"M. Prattes, I. Grishkovskaya, V.-V. Hodirnau, C. Hetzmannseder, G. Zisser, C. Sailer, V. Kargas, M. Loibl, M. Gerhalter, L. Kofler, A.J. Warren, F. Stengel, D. Haselbach, H. Bergler, Nature Structural &#38; Molecular Biology 29 (2022) 942–953.","apa":"Prattes, M., Grishkovskaya, I., Hodirnau, V.-V., Hetzmannseder, C., Zisser, G., Sailer, C., … Bergler, H. (2022). Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1. <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-022-00832-5\">https://doi.org/10.1038/s41594-022-00832-5</a>","ama":"Prattes M, Grishkovskaya I, Hodirnau V-V, et al. Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1. <i>Nature Structural &#38; Molecular Biology</i>. 2022;29(9):942-953. doi:<a href=\"https://doi.org/10.1038/s41594-022-00832-5\">10.1038/s41594-022-00832-5</a>","chicago":"Prattes, Michael, Irina Grishkovskaya, Victor-Valentin Hodirnau, Christina Hetzmannseder, Gertrude Zisser, Carolin Sailer, Vasileios Kargas, et al. “Visualizing Maturation Factor Extraction from the Nascent Ribosome by the AAA-ATPase Drg1.” <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41594-022-00832-5\">https://doi.org/10.1038/s41594-022-00832-5</a>.","ieee":"M. Prattes <i>et al.</i>, “Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1,” <i>Nature Structural &#38; Molecular Biology</i>, vol. 29, no. 9. Springer Nature, pp. 942–953, 2022."},"publication":"Nature Structural & Molecular Biology","external_id":{"pmid":["36097293"],"isi":["000852942100004"]},"file":[{"relation":"main_file","content_type":"application/pdf","access_level":"open_access","creator":"dernst","date_updated":"2023-01-30T10:00:04Z","success":1,"checksum":"2d5c3ec01718fefd7553052b0b8a0793","file_id":"12447","date_created":"2023-01-30T10:00:04Z","file_size":9935057,"file_name":"2022_NatureStrucMolecBio_Prattes.pdf"}],"title":"Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1","acknowledged_ssus":[{"_id":"EM-Fac"}],"status":"public","date_updated":"2023-08-04T09:52:20Z","publication_status":"published","page":"942-953","oa_version":"Published Version","day":"12","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"abstract":[{"lang":"eng","text":"The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large ribosomal subunit. Drg1 releases the shuttling maturation factor Rlp24 from pre-60S particles shortly after nuclear export, a strict requirement for downstream maturation. The molecular mechanism of release remained elusive. Here, we report a series of cryo-EM structures that captured the extraction of Rlp24 from pre-60S particles by Saccharomyces cerevisiae Drg1. These structures reveal that Arx1 and the eukaryote-specific rRNA expansion segment ES27 form a joint docking platform that positions Drg1 for efficient extraction of Rlp24 from the pre-ribosome. The tips of the Drg1 N domains thereby guide the Rlp24 C terminus into the central pore of the Drg1 hexamer, enabling extraction by a hand-over-hand translocation mechanism. Our results uncover substrate recognition and processing by Drg1 step by step and provide a comprehensive mechanistic picture of the conserved modus operandi of AAA-ATPases."}]},{"date_published":"2021-10-15T00:00:00Z","author":[{"orcid":"0000-0003-1548-0177","last_name":"Mühlböck","id":"6395C5F6-89DF-11E9-9C97-6BDFE5697425","first_name":"Fabian","full_name":"Mühlböck, Fabian"},{"last_name":"Tate","first_name":"Ross","full_name":"Tate, Ross"}],"oa":1,"_id":"10153","type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1145/3485504","publisher":"Association for Computing Machinery","year":"2021","article_type":"original","volume":5,"month":"10","quality_controlled":"1","publication_identifier":{"eissn":["2475-1421"]},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","ddc":["005"],"file_date_updated":"2021-10-19T12:52:23Z","conference":{"location":"Chicago, IL, United States","name":"OOPSLA: Object-Oriented Programming, Systems, Languages, and Applications","start_date":"2021-10-17","end_date":"2021-10-23"},"keyword":["gradual typing","gradual guarantee","nominal","structural","call tags"],"intvolume":"         5","date_created":"2021-10-19T12:48:44Z","article_number":"127","acknowledgement":"We thank the reviewers for their valuable suggestions towards improving the paper. We also \r\nthank Mae Milano and Adrian Sampson, as well as the members of the Programming Languages Discussion Group at Cornell University and of the Programming Research Laboratory at Northeastern University, for their helpful feedback on preliminary findings of this work.\r\n\r\nThis material is based upon work supported in part by the National Science Foundation (NSF) through grant CCF-1350182 and the Austrian Science Fund (FWF) through grant Z211-N23 (Wittgenstein~Award).\r\nAny opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF or the FWF.","department":[{"_id":"ToHe"}],"oa_version":"Published Version","publication_status":"published","tmp":{"short":"CC BY-ND (4.0)","image":"/image/cc_by_nd.png","name":"Creative Commons Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nd/4.0/legalcode"},"day":"15","abstract":[{"text":"Gradual typing is a principled means for mixing typed and untyped code. But typed and untyped code often exhibit different programming patterns. There is already substantial research investigating gradually giving types to code exhibiting typical untyped patterns, and some research investigating gradually removing types from code exhibiting typical typed patterns. This paper investigates how to extend these established gradual-typing concepts to give formal guarantees not only about how to change types as code evolves but also about how to change such programming patterns as well.\r\n\r\nIn particular, we explore mixing untyped \"structural\" code with typed \"nominal\" code in an object-oriented language. But whereas previous work only allowed \"nominal\" objects to be treated as \"structural\" objects, we also allow \"structural\" objects to dynamically acquire certain nominal types, namely interfaces. We present a calculus that supports such \"cross-paradigm\" code migration and interoperation in a manner satisfying both the static and dynamic gradual guarantees, and demonstrate that the calculus can be implemented efficiently.","lang":"eng"}],"status":"public","license":"https://creativecommons.org/licenses/by-nd/4.0/","date_updated":"2021-11-12T11:30:07Z","publication":"Proceedings of the ACM on Programming Languages","file":[{"creator":"fmuehlbo","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_name":"monnom-oopsla21.pdf","file_size":770269,"file_id":"10154","checksum":"71011efd2da771cafdec7f0d9693f8c1","date_created":"2021-10-19T12:52:23Z","date_updated":"2021-10-19T12:52:23Z","success":1}],"title":"Transitioning from structural to nominal code with efficient gradual typing","has_accepted_license":"1","project":[{"_id":"25F42A32-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z211","call_identifier":"FWF"}],"citation":{"ista":"Mühlböck F, Tate R. 2021. Transitioning from structural to nominal code with efficient gradual typing. Proceedings of the ACM on Programming Languages. 5, 127.","short":"F. Mühlböck, R. Tate, Proceedings of the ACM on Programming Languages 5 (2021).","mla":"Mühlböck, Fabian, and Ross Tate. “Transitioning from Structural to Nominal Code with Efficient Gradual Typing.” <i>Proceedings of the ACM on Programming Languages</i>, vol. 5, 127, Association for Computing Machinery, 2021, doi:<a href=\"https://doi.org/10.1145/3485504\">10.1145/3485504</a>.","apa":"Mühlböck, F., &#38; Tate, R. (2021). Transitioning from structural to nominal code with efficient gradual typing. <i>Proceedings of the ACM on Programming Languages</i>. Chicago, IL, United States: Association for Computing Machinery. <a href=\"https://doi.org/10.1145/3485504\">https://doi.org/10.1145/3485504</a>","ama":"Mühlböck F, Tate R. Transitioning from structural to nominal code with efficient gradual typing. <i>Proceedings of the ACM on Programming Languages</i>. 2021;5. doi:<a href=\"https://doi.org/10.1145/3485504\">10.1145/3485504</a>","chicago":"Mühlböck, Fabian, and Ross Tate. “Transitioning from Structural to Nominal Code with Efficient Gradual Typing.” <i>Proceedings of the ACM on Programming Languages</i>. Association for Computing Machinery, 2021. <a href=\"https://doi.org/10.1145/3485504\">https://doi.org/10.1145/3485504</a>.","ieee":"F. Mühlböck and R. Tate, “Transitioning from structural to nominal code with efficient gradual typing,” <i>Proceedings of the ACM on Programming Languages</i>, vol. 5. Association for Computing Machinery, 2021."}},{"date_published":"2021-11-03T00:00:00Z","author":[{"id":"38C393BE-F248-11E8-B48F-1D18A9856A87","last_name":"Dimchev","orcid":"0000-0001-8370-6161","first_name":"Georgi A","full_name":"Dimchev, Georgi A"},{"last_name":"Amiri","first_name":"Behnam","full_name":"Amiri, Behnam"},{"first_name":"Florian","full_name":"Fäßler, Florian","id":"404F5528-F248-11E8-B48F-1D18A9856A87","last_name":"Fäßler","orcid":"0000-0001-7149-769X"},{"full_name":"Falcke, Martin","first_name":"Martin","last_name":"Falcke"},{"full_name":"Schur, Florian KM","first_name":"Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"_id":"10290","type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1016/j.jsb.2021.107808","publisher":"Elsevier ","year":"2021","isi":1,"article_type":"original","volume":213,"month":"11","quality_controlled":"1","publication_identifier":{"issn":["1047-8477"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"Yes (via OA deal)","ddc":["572"],"file_date_updated":"2021-11-15T13:11:27Z","keyword":["Structural Biology"],"intvolume":"       213","date_created":"2021-11-15T12:21:42Z","article_number":"107808","acknowledgement":"This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), the BioImaging Facility (BIF), and the Electron Microscopy Facility (EMF). We also thank Victor-Valentin Hodirnau for help with cryo-ET data acquisition. The authors acknowledge support from IST Austria and from the Austrian Science Fund (FWF): M02495 to G.D. and Austrian Science Fund (FWF): P33367 to F.K.M.S.","department":[{"_id":"FlSc"}],"oa_version":"Published Version","publication_status":"published","day":"03","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"abstract":[{"text":"A precise quantitative description of the ultrastructural characteristics underlying biological mechanisms is often key to their understanding. This is particularly true for dynamic extra- and intracellular filamentous assemblies, playing a role in cell motility, cell integrity, cytokinesis, tissue formation and maintenance. For example, genetic manipulation or modulation of actin regulatory proteins frequently manifests in changes of the morphology, dynamics, and ultrastructural architecture of actin filament-rich cell peripheral structures, such as lamellipodia or filopodia. However, the observed ultrastructural effects often remain subtle and require sufficiently large datasets for appropriate quantitative analysis. The acquisition of such large datasets has been enabled by recent advances in high-throughput cryo-electron tomography (cryo-ET) methods. This also necessitates the development of complementary approaches to maximize the extraction of relevant biological information. We have developed a computational toolbox for the semi-automatic quantification of segmented and vectorized filamentous networks from pre-processed cryo-electron tomograms, facilitating the analysis and cross-comparison of multiple experimental conditions. GUI-based components simplify the processing of data and allow users to obtain a large number of ultrastructural parameters describing filamentous assemblies. We demonstrate the feasibility of this workflow by analyzing cryo-ET data of untreated and chemically perturbed branched actin filament networks and that of parallel actin filament arrays. In principle, the computational toolbox presented here is applicable for data analysis comprising any type of filaments in regular (i.e. parallel) or random arrangement. We show that it can ease the identification of key differences between experimental groups and facilitate the in-depth analysis of ultrastructural data in a time-efficient manner.","lang":"eng"}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"status":"public","date_updated":"2023-11-21T08:36:02Z","publication":"Journal of Structural Biology","external_id":{"isi":["000720259500002"]},"related_material":{"record":[{"id":"14502","status":"public","relation":"software"}]},"title":"Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data","file":[{"checksum":"6b209e4d44775d4e02b50f78982c15fa","date_created":"2021-11-15T13:11:27Z","file_id":"10291","date_updated":"2021-11-15T13:11:27Z","success":1,"file_name":"2021_JournalStructBiol_Dimchev.pdf","file_size":16818304,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","creator":"cchlebak"}],"issue":"4","scopus_import":"1","has_accepted_license":"1","project":[{"grant_number":"P33367","name":"Structure and isoform diversity of the Arp2/3 complex","_id":"9B954C5C-BA93-11EA-9121-9846C619BF3A"},{"name":"Protein structure and function in filopodia across scales","_id":"2674F658-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"M02495"}],"citation":{"ieee":"G. A. Dimchev, B. Amiri, F. Fäßler, M. Falcke, and F. K. Schur, “Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data,” <i>Journal of Structural Biology</i>, vol. 213, no. 4. Elsevier , 2021.","chicago":"Dimchev, Georgi A, Behnam Amiri, Florian Fäßler, Martin Falcke, and Florian KM Schur. “Computational Toolbox for Ultrastructural Quantitative Analysis of Filament Networks in Cryo-ET Data.” <i>Journal of Structural Biology</i>. Elsevier , 2021. <a href=\"https://doi.org/10.1016/j.jsb.2021.107808\">https://doi.org/10.1016/j.jsb.2021.107808</a>.","ama":"Dimchev GA, Amiri B, Fäßler F, Falcke M, Schur FK. Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data. <i>Journal of Structural Biology</i>. 2021;213(4). doi:<a href=\"https://doi.org/10.1016/j.jsb.2021.107808\">10.1016/j.jsb.2021.107808</a>","short":"G.A. Dimchev, B. Amiri, F. Fäßler, M. Falcke, F.K. Schur, Journal of Structural Biology 213 (2021).","ista":"Dimchev GA, Amiri B, Fäßler F, Falcke M, Schur FK. 2021. Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data. Journal of Structural Biology. 213(4), 107808.","apa":"Dimchev, G. A., Amiri, B., Fäßler, F., Falcke, M., &#38; Schur, F. K. (2021). Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data. <i>Journal of Structural Biology</i>. Elsevier . <a href=\"https://doi.org/10.1016/j.jsb.2021.107808\">https://doi.org/10.1016/j.jsb.2021.107808</a>","mla":"Dimchev, Georgi A., et al. “Computational Toolbox for Ultrastructural Quantitative Analysis of Filament Networks in Cryo-ET Data.” <i>Journal of Structural Biology</i>, vol. 213, no. 4, 107808, Elsevier , 2021, doi:<a href=\"https://doi.org/10.1016/j.jsb.2021.107808\">10.1016/j.jsb.2021.107808</a>."}},{"date_published":"2020-01-06T00:00:00Z","author":[{"last_name":"Rampelt","full_name":"Rampelt, Heike","first_name":"Heike"},{"first_name":"Iva","full_name":"Sucec, Iva","last_name":"Sucec"},{"last_name":"Bersch","first_name":"Beate","full_name":"Bersch, Beate"},{"first_name":"Patrick","full_name":"Horten, Patrick","last_name":"Horten"},{"last_name":"Perschil","full_name":"Perschil, Inge","first_name":"Inge"},{"full_name":"Martinou, Jean-Claude","first_name":"Jean-Claude","last_name":"Martinou"},{"last_name":"van der Laan","first_name":"Martin","full_name":"van der Laan, Martin"},{"last_name":"Wiedemann","full_name":"Wiedemann, Nils","first_name":"Nils"},{"id":"7B541462-FAF6-11E9-A490-E8DFE5697425","last_name":"Schanda","orcid":"0000-0002-9350-7606","full_name":"Schanda, Paul","first_name":"Paul"},{"full_name":"Pfanner, Nikolaus","first_name":"Nikolaus","last_name":"Pfanner"}],"oa":1,"_id":"8402","type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1186/s12915-019-0733-6","publisher":"Springer Nature","year":"2020","volume":18,"article_type":"original","month":"01","quality_controlled":"1","publication_identifier":{"issn":["1741-7007"]},"extern":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","keyword":["Biotechnology","Plant Science","General Biochemistry","Genetics and Molecular Biology","Developmental Biology","Cell Biology","Physiology","Ecology","Evolution","Behavior and Systematics","Structural Biology","General Agricultural and Biological Sciences"],"intvolume":"        18","article_number":"2","date_created":"2020-09-17T10:26:53Z","pmid":1,"publication_status":"published","oa_version":"Published Version","day":"06","abstract":[{"text":"Background: The mitochondrial pyruvate carrier (MPC) plays a central role in energy metabolism by transporting pyruvate across the inner mitochondrial membrane. Its heterodimeric composition and homology to SWEET and semiSWEET transporters set the MPC apart from the canonical mitochondrial carrier family (named MCF or SLC25). The import of the canonical carriers is mediated by the carrier translocase of the inner membrane (TIM22) pathway and is dependent on their structure, which features an even number of transmembrane segments and both termini in the intermembrane space. The import pathway of MPC proteins has not been elucidated. The odd number of transmembrane segments and positioning of the N-terminus in the matrix argues against an import via the TIM22 carrier pathway but favors an import via the flexible presequence pathway.\r\nResults: Here, we systematically analyzed the import pathways of Mpc2 and Mpc3 and report that, contrary to an expected import via the flexible presequence pathway, yeast MPC proteins with an odd number of transmembrane segments and matrix-exposed N-terminus are imported by the carrier pathway, using the receptor Tom70, small TIM chaperones, and the TIM22 complex. The TIM9·10 complex chaperones MPC proteins through the mitochondrial intermembrane space using conserved hydrophobic motifs that are also required for the interaction with canonical carrier proteins.\r\nConclusions: The carrier pathway can import paired and non-paired transmembrane helices and translocate N-termini to either side of the mitochondrial inner membrane, revealing an unexpected versatility of the mitochondrial import pathway for non-cleavable inner membrane proteins.","lang":"eng"}],"status":"public","date_updated":"2021-01-12T08:19:02Z","publication":"BMC Biology","external_id":{"pmid":["31907035"]},"title":"The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments","main_file_link":[{"url":"https://doi.org/10.1186/s12915-019-0733-6","open_access":"1"}],"citation":{"ama":"Rampelt H, Sucec I, Bersch B, et al. The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments. <i>BMC Biology</i>. 2020;18. doi:<a href=\"https://doi.org/10.1186/s12915-019-0733-6\">10.1186/s12915-019-0733-6</a>","apa":"Rampelt, H., Sucec, I., Bersch, B., Horten, P., Perschil, I., Martinou, J.-C., … Pfanner, N. (2020). The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments. <i>BMC Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s12915-019-0733-6\">https://doi.org/10.1186/s12915-019-0733-6</a>","short":"H. Rampelt, I. Sucec, B. Bersch, P. Horten, I. Perschil, J.-C. Martinou, M. van der Laan, N. Wiedemann, P. Schanda, N. Pfanner, BMC Biology 18 (2020).","mla":"Rampelt, Heike, et al. “The Mitochondrial Carrier Pathway Transports Non-Canonical Substrates with an Odd Number of Transmembrane Segments.” <i>BMC Biology</i>, vol. 18, 2, Springer Nature, 2020, doi:<a href=\"https://doi.org/10.1186/s12915-019-0733-6\">10.1186/s12915-019-0733-6</a>.","ista":"Rampelt H, Sucec I, Bersch B, Horten P, Perschil I, Martinou J-C, van der Laan M, Wiedemann N, Schanda P, Pfanner N. 2020. The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments. BMC Biology. 18, 2.","ieee":"H. Rampelt <i>et al.</i>, “The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments,” <i>BMC Biology</i>, vol. 18. Springer Nature, 2020.","chicago":"Rampelt, Heike, Iva Sucec, Beate Bersch, Patrick Horten, Inge Perschil, Jean-Claude Martinou, Martin van der Laan, Nils Wiedemann, Paul Schanda, and Nikolaus Pfanner. “The Mitochondrial Carrier Pathway Transports Non-Canonical Substrates with an Odd Number of Transmembrane Segments.” <i>BMC Biology</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1186/s12915-019-0733-6\">https://doi.org/10.1186/s12915-019-0733-6</a>."}},{"doi":"10.1016/j.jmb.2020.09.001","language":[{"iso":"eng"}],"year":"2020","publisher":"Elsevier","type":"journal_article","author":[{"full_name":"Rosa, Higor Vinícius Dias","first_name":"Higor Vinícius Dias","last_name":"Rosa"},{"full_name":"Leonardo, Diego Antonio","first_name":"Diego Antonio","last_name":"Leonardo"},{"last_name":"Brognara","id":"D96FFDA0-A884-11E9-9968-DC26E6697425","full_name":"Brognara, Gabriel","first_name":"Gabriel"},{"first_name":"José","full_name":"Brandão-Neto, José","last_name":"Brandão-Neto"},{"first_name":"Humberto","full_name":"D'Muniz Pereira, Humberto","last_name":"D'Muniz Pereira"},{"last_name":"Araújo","full_name":"Araújo, Ana Paula Ulian","first_name":"Ana Paula Ulian"},{"last_name":"Garratt","full_name":"Garratt, Richard Charles","first_name":"Richard Charles"}],"_id":"15036","oa":1,"date_published":"2020-10-02T00:00:00Z","date_created":"2024-02-28T08:50:34Z","department":[{"_id":"MaLo"}],"pmid":1,"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"       432","keyword":["Molecular Biology","Structural Biology"],"month":"10","publication_identifier":{"issn":["0022-2836"]},"quality_controlled":"1","article_type":"original","volume":432,"date_updated":"2024-02-28T12:37:54Z","status":"public","day":"02","publication_status":"published","page":"5784-5801","oa_version":"Published Version","abstract":[{"text":"The assembly of a septin filament requires that homologous monomers must distinguish between one another in establishing appropriate interfaces with their neighbors. To understand this phenomenon at the molecular level, we present the first four crystal structures of heterodimeric septin complexes. We describe in detail the two distinct types of G-interface present within the octameric particles, which must polymerize to form filaments. These are formed between SEPT2 and SEPT6 and between SEPT7 and SEPT3, and their description permits an understanding of the structural basis for the selectivity necessary for correct filament assembly. By replacing SEPT6 by SEPT8 or SEPT11, it is possible to rationalize Kinoshita's postulate, which predicts the exchangeability of septins from within a subgroup. Switches I and II, which in classical small GTPases provide a mechanism for nucleotide-dependent conformational change, have been repurposed in septins to play a fundamental role in molecular recognition. Specifically, it is switch I which holds the key to discriminating between the two different G-interfaces. Moreover, residues which are characteristic for a given subgroup play subtle, but pivotal, roles in guaranteeing that the correct interfaces are formed.","lang":"eng"}],"citation":{"ama":"Rosa HVD, Leonardo DA, Brognara G, et al. Molecular recognition at septin interfaces: The switches hold the key. <i>Journal of Molecular Biology</i>. 2020;432(21):5784-5801. doi:<a href=\"https://doi.org/10.1016/j.jmb.2020.09.001\">10.1016/j.jmb.2020.09.001</a>","ista":"Rosa HVD, Leonardo DA, Brognara G, Brandão-Neto J, D’Muniz Pereira H, Araújo APU, Garratt RC. 2020. Molecular recognition at septin interfaces: The switches hold the key. Journal of Molecular Biology. 432(21), 5784–5801.","short":"H.V.D. Rosa, D.A. Leonardo, G. Brognara, J. Brandão-Neto, H. D’Muniz Pereira, A.P.U. Araújo, R.C. Garratt, Journal of Molecular Biology 432 (2020) 5784–5801.","mla":"Rosa, Higor Vinícius Dias, et al. “Molecular Recognition at Septin Interfaces: The Switches Hold the Key.” <i>Journal of Molecular Biology</i>, vol. 432, no. 21, Elsevier, 2020, pp. 5784–801, doi:<a href=\"https://doi.org/10.1016/j.jmb.2020.09.001\">10.1016/j.jmb.2020.09.001</a>.","apa":"Rosa, H. V. D., Leonardo, D. A., Brognara, G., Brandão-Neto, J., D’Muniz Pereira, H., Araújo, A. P. U., &#38; Garratt, R. C. (2020). Molecular recognition at septin interfaces: The switches hold the key. <i>Journal of Molecular Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jmb.2020.09.001\">https://doi.org/10.1016/j.jmb.2020.09.001</a>","ieee":"H. V. D. Rosa <i>et al.</i>, “Molecular recognition at septin interfaces: The switches hold the key,” <i>Journal of Molecular Biology</i>, vol. 432, no. 21. Elsevier, pp. 5784–5801, 2020.","chicago":"Rosa, Higor Vinícius Dias, Diego Antonio Leonardo, Gabriel Brognara, José Brandão-Neto, Humberto D’Muniz Pereira, Ana Paula Ulian Araújo, and Richard Charles Garratt. “Molecular Recognition at Septin Interfaces: The Switches Hold the Key.” <i>Journal of Molecular Biology</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.jmb.2020.09.001\">https://doi.org/10.1016/j.jmb.2020.09.001</a>."},"issue":"21","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.jmb.2020.09.001"}],"publication":"Journal of Molecular Biology","title":"Molecular recognition at septin interfaces: The switches hold the key","external_id":{"pmid":["32910969"]}},{"volume":206,"article_type":"original","month":"04","publication_identifier":{"issn":["1047-8477"]},"quality_controlled":"1","article_processing_charge":"No","extern":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"       206","keyword":["Structural Biology"],"date_created":"2020-09-17T10:29:10Z","pmid":1,"date_published":"2019-04-01T00:00:00Z","author":[{"last_name":"Bougault","first_name":"Catherine","full_name":"Bougault, Catherine"},{"first_name":"Isabel","full_name":"Ayala, Isabel","last_name":"Ayala"},{"full_name":"Vollmer, Waldemar","first_name":"Waldemar","last_name":"Vollmer"},{"last_name":"Simorre","full_name":"Simorre, Jean-Pierre","first_name":"Jean-Pierre"},{"full_name":"Schanda, Paul","first_name":"Paul","last_name":"Schanda","id":"7B541462-FAF6-11E9-A490-E8DFE5697425","orcid":"0000-0002-9350-7606"}],"_id":"8409","type":"journal_article","doi":"10.1016/j.jsb.2018.07.009","language":[{"iso":"eng"}],"year":"2019","publisher":"Elsevier","publication":"Journal of Structural Biology","title":"Studying intact bacterial peptidoglycan by proton-detected NMR spectroscopy at 100 kHz MAS frequency","external_id":{"pmid":["30031884"]},"issue":"1","citation":{"ieee":"C. Bougault, I. Ayala, W. Vollmer, J.-P. Simorre, and P. Schanda, “Studying intact bacterial peptidoglycan by proton-detected NMR spectroscopy at 100 kHz MAS frequency,” <i>Journal of Structural Biology</i>, vol. 206, no. 1. Elsevier, pp. 66–72, 2019.","chicago":"Bougault, Catherine, Isabel Ayala, Waldemar Vollmer, Jean-Pierre Simorre, and Paul Schanda. “Studying Intact Bacterial Peptidoglycan by Proton-Detected NMR Spectroscopy at 100 kHz MAS Frequency.” <i>Journal of Structural Biology</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.jsb.2018.07.009\">https://doi.org/10.1016/j.jsb.2018.07.009</a>.","ama":"Bougault C, Ayala I, Vollmer W, Simorre J-P, Schanda P. Studying intact bacterial peptidoglycan by proton-detected NMR spectroscopy at 100 kHz MAS frequency. <i>Journal of Structural Biology</i>. 2019;206(1):66-72. doi:<a href=\"https://doi.org/10.1016/j.jsb.2018.07.009\">10.1016/j.jsb.2018.07.009</a>","mla":"Bougault, Catherine, et al. “Studying Intact Bacterial Peptidoglycan by Proton-Detected NMR Spectroscopy at 100 kHz MAS Frequency.” <i>Journal of Structural Biology</i>, vol. 206, no. 1, Elsevier, 2019, pp. 66–72, doi:<a href=\"https://doi.org/10.1016/j.jsb.2018.07.009\">10.1016/j.jsb.2018.07.009</a>.","apa":"Bougault, C., Ayala, I., Vollmer, W., Simorre, J.-P., &#38; Schanda, P. (2019). Studying intact bacterial peptidoglycan by proton-detected NMR spectroscopy at 100 kHz MAS frequency. <i>Journal of Structural Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jsb.2018.07.009\">https://doi.org/10.1016/j.jsb.2018.07.009</a>","ista":"Bougault C, Ayala I, Vollmer W, Simorre J-P, Schanda P. 2019. Studying intact bacterial peptidoglycan by proton-detected NMR spectroscopy at 100 kHz MAS frequency. Journal of Structural Biology. 206(1), 66–72.","short":"C. Bougault, I. Ayala, W. Vollmer, J.-P. Simorre, P. Schanda, Journal of Structural Biology 206 (2019) 66–72."},"day":"01","publication_status":"published","page":"66-72","oa_version":"Submitted Version","abstract":[{"text":"The bacterial cell wall is composed of the peptidoglycan (PG), a large polymer that maintains the integrity of the bacterial cell. Due to its multi-gigadalton size, heterogeneity, and dynamics, atomic-resolution studies are inherently complex. Solid-state NMR is an important technique to gain insight into its structure, dynamics and interactions. Here, we explore the possibilities to study the PG with ultra-fast (100 kHz) magic-angle spinning NMR. We demonstrate that highly resolved spectra can be obtained, and show strategies to obtain site-specific resonance assignments and distance information. We also explore the use of proton-proton correlation experiments, thus opening the way for NMR studies of intact cell walls without the need for isotope labeling.","lang":"eng"}],"status":"public","date_updated":"2021-01-12T08:19:05Z"},{"date_updated":"2023-09-07T13:18:26Z","status":"public","abstract":[{"lang":"eng","text":"Motivated by fixed-parameter tractable (FPT) problems in computational topology, we consider the treewidth tw(M) of a compact, connected 3-manifold M, defined to be the minimum treewidth of the face pairing graph of any triangulation T of M. In this setting the relationship between the topology of a 3-manifold and its treewidth is of particular interest. First, as a corollary of work of Jaco and Rubinstein, we prove that for any closed, orientable 3-manifold M the treewidth tw(M) is at most 4g(M)-2, where g(M) denotes Heegaard genus of M. In combination with our earlier work with Wagner, this yields that for non-Haken manifolds the Heegaard genus and the treewidth are within a constant factor. Second, we characterize all 3-manifolds of treewidth one: These are precisely the lens spaces and a single other Seifert fibered space. Furthermore, we show that all remaining orientable Seifert fibered spaces over the 2-sphere or a non-orientable surface have treewidth two. In particular, for every spherical 3-manifold we exhibit a triangulation of treewidth at most two. Our results further validate the parameter of treewidth (and other related parameters such as cutwidth or congestion) to be useful for topological computing, and also shed more light on the scope of existing FPT-algorithms in the field."}],"page":"44:1-44:20","publication_status":"published","oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"01","arxiv":1,"citation":{"chicago":"Huszár, Kristóf, and Jonathan Spreer. “3-Manifold Triangulations with Small Treewidth.” In <i>35th International Symposium on Computational Geometry</i>, 129:44:1-44:20. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019. <a href=\"https://doi.org/10.4230/LIPIcs.SoCG.2019.44\">https://doi.org/10.4230/LIPIcs.SoCG.2019.44</a>.","ieee":"K. Huszár and J. Spreer, “3-manifold triangulations with small treewidth,” in <i>35th International Symposium on Computational Geometry</i>, Portland, Oregon, United States, 2019, vol. 129, p. 44:1-44:20.","mla":"Huszár, Kristóf, and Jonathan Spreer. “3-Manifold Triangulations with Small Treewidth.” <i>35th International Symposium on Computational Geometry</i>, vol. 129, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019, p. 44:1-44:20, doi:<a href=\"https://doi.org/10.4230/LIPIcs.SoCG.2019.44\">10.4230/LIPIcs.SoCG.2019.44</a>.","ista":"Huszár K, Spreer J. 2019. 3-manifold triangulations with small treewidth. 35th International Symposium on Computational Geometry. SoCG: Symposium on Computational Geometry, LIPIcs, vol. 129, 44:1-44:20.","short":"K. Huszár, J. Spreer, in:, 35th International Symposium on Computational Geometry, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019, p. 44:1-44:20.","apa":"Huszár, K., &#38; Spreer, J. (2019). 3-manifold triangulations with small treewidth. In <i>35th International Symposium on Computational Geometry</i> (Vol. 129, p. 44:1-44:20). Portland, Oregon, United States: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. <a href=\"https://doi.org/10.4230/LIPIcs.SoCG.2019.44\">https://doi.org/10.4230/LIPIcs.SoCG.2019.44</a>","ama":"Huszár K, Spreer J. 3-manifold triangulations with small treewidth. In: <i>35th International Symposium on Computational Geometry</i>. Vol 129. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2019:44:1-44:20. doi:<a href=\"https://doi.org/10.4230/LIPIcs.SoCG.2019.44\">10.4230/LIPIcs.SoCG.2019.44</a>"},"alternative_title":["LIPIcs"],"has_accepted_license":"1","scopus_import":"1","related_material":{"record":[{"relation":"part_of_dissertation","id":"8032","status":"public"}]},"external_id":{"arxiv":["1812.05528"]},"title":"3-manifold triangulations with small treewidth","file":[{"date_created":"2019-06-12T06:45:33Z","file_id":"6557","checksum":"29d18c435368468aa85823dabb157e43","date_updated":"2020-07-14T12:47:33Z","file_name":"2019_LIPIcs-Huszar.pdf","file_size":905885,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","creator":"kschuh"}],"publication":"35th International Symposium on Computational Geometry","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","year":"2019","language":[{"iso":"eng"}],"doi":"10.4230/LIPIcs.SoCG.2019.44","type":"conference","oa":1,"_id":"6556","author":[{"first_name":"Kristóf","full_name":"Huszár, Kristóf","orcid":"0000-0002-5445-5057","id":"33C26278-F248-11E8-B48F-1D18A9856A87","last_name":"Huszár"},{"full_name":"Spreer, Jonathan","first_name":"Jonathan","last_name":"Spreer"}],"date_published":"2019-06-01T00:00:00Z","department":[{"_id":"UlWa"}],"date_created":"2019-06-11T20:09:57Z","keyword":["computational 3-manifold topology","fixed-parameter tractability","layered triangulations","structural graph theory","treewidth","cutwidth","Heegaard genus"],"intvolume":"       129","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["516"],"article_processing_charge":"No","conference":{"location":"Portland, Oregon, United States","name":"SoCG: Symposium on Computational Geometry","start_date":"2019-06-18","end_date":"2019-06-21"},"file_date_updated":"2020-07-14T12:47:33Z","quality_controlled":"1","publication_identifier":{"isbn":["978-3-95977-104-7"],"issn":["1868-8969"]},"month":"06","volume":129},{"pmid":1,"acknowledgement":"We acknowledge funding from EPSRC (A.E.H. and A.Š.), the Academy of Medical Sciences (J.K. and A.Š.), the Wellcome Trust (J.K. and A.Š.), and the Royal Society (A.Š.). We thank Shiladitya Banerjee and Nikola Ojkic for critically reading the manuscript, and Claudia Flandoli for helping us with figures and illustrations.","date_created":"2021-11-26T11:33:21Z","keyword":["molecular biology","structural biology"],"intvolume":"        58","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","extern":"1","quality_controlled":"1","publication_identifier":{"issn":["0959-440X"]},"month":"06","article_type":"original","volume":58,"publisher":"Elsevier","year":"2019","language":[{"iso":"eng"}],"doi":"10.1016/j.sbi.2019.05.018","type":"journal_article","oa":1,"_id":"10355","author":[{"last_name":"Hafner","first_name":"Anne E","full_name":"Hafner, Anne E"},{"last_name":"Krausser","first_name":"Johannes","full_name":"Krausser, Johannes"},{"orcid":"0000-0002-7854-2139","last_name":"Šarić","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","first_name":"Anđela","full_name":"Šarić, Anđela"}],"date_published":"2019-06-18T00:00:00Z","citation":{"ista":"Hafner AE, Krausser J, Šarić A. 2019. Minimal coarse-grained models for molecular self-organisation in biology. Current Opinion in Structural Biology. 58, 43–52.","apa":"Hafner, A. E., Krausser, J., &#38; Šarić, A. (2019). Minimal coarse-grained models for molecular self-organisation in biology. <i>Current Opinion in Structural Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.sbi.2019.05.018\">https://doi.org/10.1016/j.sbi.2019.05.018</a>","mla":"Hafner, Anne E., et al. “Minimal Coarse-Grained Models for Molecular Self-Organisation in Biology.” <i>Current Opinion in Structural Biology</i>, vol. 58, Elsevier, 2019, pp. 43–52, doi:<a href=\"https://doi.org/10.1016/j.sbi.2019.05.018\">10.1016/j.sbi.2019.05.018</a>.","short":"A.E. Hafner, J. Krausser, A. Šarić, Current Opinion in Structural Biology 58 (2019) 43–52.","ama":"Hafner AE, Krausser J, Šarić A. Minimal coarse-grained models for molecular self-organisation in biology. <i>Current Opinion in Structural Biology</i>. 2019;58:43-52. doi:<a href=\"https://doi.org/10.1016/j.sbi.2019.05.018\">10.1016/j.sbi.2019.05.018</a>","chicago":"Hafner, Anne E, Johannes Krausser, and Anđela Šarić. “Minimal Coarse-Grained Models for Molecular Self-Organisation in Biology.” <i>Current Opinion in Structural Biology</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.sbi.2019.05.018\">https://doi.org/10.1016/j.sbi.2019.05.018</a>.","ieee":"A. E. Hafner, J. Krausser, and A. Šarić, “Minimal coarse-grained models for molecular self-organisation in biology,” <i>Current Opinion in Structural Biology</i>, vol. 58. Elsevier, pp. 43–52, 2019."},"scopus_import":"1","main_file_link":[{"url":"https://arxiv.org/abs/1906.09349","open_access":"1"}],"external_id":{"pmid":["31226513"]},"title":"Minimal coarse-grained models for molecular self-organisation in biology","publication":"Current Opinion in Structural Biology","date_updated":"2021-11-26T11:54:25Z","status":"public","abstract":[{"text":"The molecular machinery of life is largely created via self-organisation of individual molecules into functional assemblies. Minimal coarse-grained models, in which a whole macromolecule is represented by a small number of particles, can be of great value in identifying the main driving forces behind self-organisation in cell biology. Such models can incorporate data from both molecular and continuum scales, and their results can be directly compared to experiments. Here we review the state of the art of models for studying the formation and biological function of macromolecular assemblies in living organisms. We outline the key ingredients of each model and their main findings. We illustrate the contribution of this class of simulations to identifying the physical mechanisms behind life and diseases, and discuss their future developments.","lang":"eng"}],"oa_version":"Preprint","publication_status":"published","page":"43-52","day":"18"},{"quality_controlled":"1","publication_identifier":{"issn":["1545-9993","1545-9985"]},"month":"09","article_type":"letter_note","volume":25,"title":"Dynamics and interactions of AAC3 in DPC are not functionally relevant","publication":"Nature Structural & Molecular Biology","citation":{"chicago":"Kurauskas, Vilius, Audrey Hessel, François Dehez, Christophe Chipot, Beate Bersch, and Paul Schanda. “Dynamics and Interactions of AAC3 in DPC Are Not Functionally Relevant.” <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature, 2018. <a href=\"https://doi.org/10.1038/s41594-018-0127-4\">https://doi.org/10.1038/s41594-018-0127-4</a>.","ieee":"V. Kurauskas, A. Hessel, F. Dehez, C. Chipot, B. Bersch, and P. Schanda, “Dynamics and interactions of AAC3 in DPC are not functionally relevant,” <i>Nature Structural &#38; Molecular Biology</i>, vol. 25, no. 9. Springer Nature, pp. 745–747, 2018.","apa":"Kurauskas, V., Hessel, A., Dehez, F., Chipot, C., Bersch, B., &#38; Schanda, P. (2018). Dynamics and interactions of AAC3 in DPC are not functionally relevant. <i>Nature Structural &#38; Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-018-0127-4\">https://doi.org/10.1038/s41594-018-0127-4</a>","ista":"Kurauskas V, Hessel A, Dehez F, Chipot C, Bersch B, Schanda P. 2018. Dynamics and interactions of AAC3 in DPC are not functionally relevant. Nature Structural &#38; Molecular Biology. 25(9), 745–747.","mla":"Kurauskas, Vilius, et al. “Dynamics and Interactions of AAC3 in DPC Are Not Functionally Relevant.” <i>Nature Structural &#38; Molecular Biology</i>, vol. 25, no. 9, Springer Nature, 2018, pp. 745–47, doi:<a href=\"https://doi.org/10.1038/s41594-018-0127-4\">10.1038/s41594-018-0127-4</a>.","short":"V. Kurauskas, A. Hessel, F. Dehez, C. Chipot, B. Bersch, P. Schanda, Nature Structural &#38; Molecular Biology 25 (2018) 745–747.","ama":"Kurauskas V, Hessel A, Dehez F, Chipot C, Bersch B, Schanda P. Dynamics and interactions of AAC3 in DPC are not functionally relevant. <i>Nature Structural &#38; Molecular Biology</i>. 2018;25(9):745-747. doi:<a href=\"https://doi.org/10.1038/s41594-018-0127-4\">10.1038/s41594-018-0127-4</a>"},"date_created":"2020-09-18T10:04:59Z","keyword":["Molecular Biology","Structural Biology"],"intvolume":"        25","article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"9","extern":"1","_id":"8438","author":[{"first_name":"Vilius","full_name":"Kurauskas, Vilius","last_name":"Kurauskas"},{"last_name":"Hessel","full_name":"Hessel, Audrey","first_name":"Audrey"},{"full_name":"Dehez, François","first_name":"François","last_name":"Dehez"},{"full_name":"Chipot, Christophe","first_name":"Christophe","last_name":"Chipot"},{"full_name":"Bersch, Beate","first_name":"Beate","last_name":"Bersch"},{"orcid":"0000-0002-9350-7606","last_name":"Schanda","id":"7B541462-FAF6-11E9-A490-E8DFE5697425","first_name":"Paul","full_name":"Schanda, Paul"}],"date_published":"2018-09-03T00:00:00Z","page":"745-747","oa_version":"None","publication_status":"published","day":"03","publisher":"Springer Nature","date_updated":"2021-01-12T08:19:16Z","year":"2018","language":[{"iso":"eng"}],"doi":"10.1038/s41594-018-0127-4","type":"journal_article","status":"public"}]