[{"publication_identifier":{"eissn":["1553-7374"],"issn":["1553-7366"]},"publication_status":"published","file_date_updated":"2023-09-06T06:41:52Z","has_accepted_license":"1","intvolume":"        19","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"lang":"eng","text":"Toscana virus is a major cause of arboviral disease in humans in the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons and cell lines, we found that virus binding to the cell surface was specific, and 50% of bound virions were endocytosed within 10 min. Virions entered Rab5a+ early endosomes and, subsequently, Rab7a+ and LAMP-1+ late endosomal compartments. Penetration required intact late endosomes and occurred within 30 min following internalization. Virus entry relied on vacuolar acidification, with an optimal pH for viral membrane fusion at pH 5.5. The pH threshold increased to 5.8 with longer pre-exposure of virions to the slightly acidic pH in early endosomes. Strikingly, the particles remained infectious after entering late endosomes with a pH below the fusion threshold. Overall, our study establishes Toscana virus as a late-penetrating virus and reveals an atypical use of vacuolar acidity by this virus to enter host cells."}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"volume":19,"article_type":"original","date_created":"2023-09-03T22:01:14Z","author":[{"last_name":"Koch","full_name":"Koch, Jana","first_name":"Jana"},{"first_name":"Qilin","full_name":"Xin, Qilin","last_name":"Xin"},{"last_name":"Obr","full_name":"Obr, Martin","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","first_name":"Martin","orcid":"0000-0003-1756-6564"},{"full_name":"Schäfer, Alicia","last_name":"Schäfer","first_name":"Alicia"},{"last_name":"Rolfs","full_name":"Rolfs, Nina","first_name":"Nina"},{"full_name":"Anagho, Holda A.","last_name":"Anagho","first_name":"Holda A."},{"last_name":"Kudulyte","full_name":"Kudulyte, Aiste","first_name":"Aiste"},{"full_name":"Woltereck, Lea","last_name":"Woltereck","first_name":"Lea"},{"full_name":"Kummer, Susann","last_name":"Kummer","first_name":"Susann"},{"first_name":"Joaquin","last_name":"Campos","full_name":"Campos, Joaquin"},{"last_name":"Uckeley","full_name":"Uckeley, Zina M.","first_name":"Zina M."},{"first_name":"Lesley","full_name":"Bell-Sakyi, Lesley","last_name":"Bell-Sakyi"},{"full_name":"Kräusslich, Hans Georg","last_name":"Kräusslich","first_name":"Hans Georg"},{"last_name":"Schur","full_name":"Schur, Florian Km","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078","first_name":"Florian Km"},{"full_name":"Acuna, Claudio","last_name":"Acuna","first_name":"Claudio"},{"last_name":"Lozach","full_name":"Lozach, Pierre Yves","first_name":"Pierre Yves"}],"scopus_import":"1","day":"14","title":"The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells","oa_version":"Published Version","issue":"8","citation":{"ama":"Koch J, Xin Q, Obr M, et al. The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells. <i>PLoS Pathogens</i>. 2023;19(8). doi:<a href=\"https://doi.org/10.1371/journal.ppat.1011562\">10.1371/journal.ppat.1011562</a>","short":"J. Koch, Q. Xin, M. Obr, A. Schäfer, N. Rolfs, H.A. Anagho, A. Kudulyte, L. Woltereck, S. Kummer, J. Campos, Z.M. Uckeley, L. Bell-Sakyi, H.G. Kräusslich, F.K. Schur, C. Acuna, P.Y. Lozach, PLoS Pathogens 19 (2023).","ieee":"J. Koch <i>et al.</i>, “The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells,” <i>PLoS Pathogens</i>, vol. 19, no. 8. Public Library of Science, 2023.","chicago":"Koch, Jana, Qilin Xin, Martin Obr, Alicia Schäfer, Nina Rolfs, Holda A. Anagho, Aiste Kudulyte, et al. “The Phenuivirus Toscana Virus Makes an Atypical Use of Vacuolar Acidity to Enter Host Cells.” <i>PLoS Pathogens</i>. Public Library of Science, 2023. <a href=\"https://doi.org/10.1371/journal.ppat.1011562\">https://doi.org/10.1371/journal.ppat.1011562</a>.","ista":"Koch J, Xin Q, Obr M, Schäfer A, Rolfs N, Anagho HA, Kudulyte A, Woltereck L, Kummer S, Campos J, Uckeley ZM, Bell-Sakyi L, Kräusslich HG, Schur FK, Acuna C, Lozach PY. 2023. The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells. PLoS Pathogens. 19(8), e1011562.","mla":"Koch, Jana, et al. “The Phenuivirus Toscana Virus Makes an Atypical Use of Vacuolar Acidity to Enter Host Cells.” <i>PLoS Pathogens</i>, vol. 19, no. 8, e1011562, Public Library of Science, 2023, doi:<a href=\"https://doi.org/10.1371/journal.ppat.1011562\">10.1371/journal.ppat.1011562</a>.","apa":"Koch, J., Xin, Q., Obr, M., Schäfer, A., Rolfs, N., Anagho, H. A., … Lozach, P. Y. (2023). The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells. <i>PLoS Pathogens</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.ppat.1011562\">https://doi.org/10.1371/journal.ppat.1011562</a>"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"FlSc"}],"article_number":"e1011562","file":[{"file_id":"14269","file_size":4458336,"date_created":"2023-09-06T06:41:52Z","creator":"dernst","date_updated":"2023-09-06T06:41:52Z","relation":"main_file","checksum":"47ca3bb54b27f28b05644be0ad064bc6","success":1,"file_name":"2023_PloSPathogens_Koch.pdf","access_level":"open_access","content_type":"application/pdf"}],"month":"08","quality_controlled":"1","ddc":["570"],"date_updated":"2023-12-13T12:22:22Z","_id":"14255","type":"journal_article","doi":"10.1371/journal.ppat.1011562","article_processing_charge":"Yes","publisher":"Public Library of Science","pmid":1,"acknowledgement":"We acknowledge Elodie Chatre and the Imaging Platform Platim, SFR Biosciences, Lyon, as well as Vibor Laketa and the Infectious Diseases Imaging Platform (IDIP) at the Center for Integrative Infectious Disease Research (CIID) Heidelberg. The sand fly cell lines were supplied by the Tick Cell Biobank at the University of Liverpool. F.K.M.S. acknowledges support from the Scientific Service Units (SSUs) of ISTA through resources provided by the Electron Microscopy Facility (EMF).\r\nThis work was supported by CellNetworks Research Group funds and Deutsche Forschungsgemeinschaft (DFG) funding (LO-2338/3-1) and the Agence Nationale de la Recherche (ANR) funding (grant numbers ANR-21-CE11-0012 and ANR-22-CE15-0034), all awarded to P.-Y.L. This work was also supported by the LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon (UDL), within the program “Investissements d’Avenir” (ANR-11-IDEX-0007) operated by the ANR and by the RESPOND program of the UDL (awarded to P.-Y.L) . C.A. was supported by the Chica and Heinz Schaller Research Group funds, NARSAD 2019 award, a Fritz Thyssen Research Grant, and the SFB1158-S02 grant. L.B-S. is supported by a United Kingdom Biotechnology and Biological Sciences Research Council grant (BB/P024270/1) and a Wellcome Trust grant (223743/Z/21/Z). F.K.M.S acknowledges support from the Austrian Science Fund (FWF, P31445). J.K. received a salary from the DFG (LO-2338/3-1) and then from the ANR (ANR-11-LABX-0048). The salary of Z.M.U. was partially covered by the DFG (LO-2338/3-1). S.K. received a salary from the DFG (SFB1129). We are grateful to the Chinese Scholarship Council (CSC; 201904910701), DAAD/ANID (57451854/62180003), the Rufus A. Kellogg fellowship program (Amherst College, Massachusetts, USA) for awarding fellowships to Q.X., J.C., and H.A.A., respectively.","date_published":"2023-08-14T00:00:00Z","project":[{"call_identifier":"FWF","grant_number":"P31445","name":"Structural conservation and diversity in retroviral capsid","_id":"26736D6A-B435-11E9-9278-68D0E5697425"}],"status":"public","publication":"PLoS Pathogens","isi":1,"year":"2023","external_id":{"pmid":["37578957"],"isi":["001050846300004"]}},{"ddc":["570"],"quality_controlled":"1","article_processing_charge":"Yes (via OA deal)","doi":"10.1016/j.jsb.2022.107852","publisher":"Elsevier","_id":"11155","date_updated":"2023-08-03T06:25:23Z","type":"journal_article","status":"public","publication":"Journal of Structural Biology","project":[{"_id":"26736D6A-B435-11E9-9278-68D0E5697425","name":"Structural conservation and diversity in retroviral capsid","grant_number":"P31445","call_identifier":"FWF"}],"pmid":1,"date_published":"2022-06-01T00:00:00Z","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.","isi":1,"year":"2022","external_id":{"pmid":["35351542"],"isi":["000790733600001"]},"keyword":["Structural Biology"],"has_accepted_license":"1","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"EM-Fac"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"       214","abstract":[{"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.","lang":"eng"}],"file_date_updated":"2022-08-02T11:07:58Z","publication_identifier":{"issn":["1047-8477"]},"publication_status":"published","scopus_import":"1","day":"01","author":[{"id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","full_name":"Obr, Martin","last_name":"Obr","first_name":"Martin"},{"last_name":"Hagen","full_name":"Hagen, Wim J.H.","first_name":"Wim J.H."},{"first_name":"Robert A.","last_name":"Dick","full_name":"Dick, Robert A."},{"full_name":"Yu, Lingbo","last_name":"Yu","first_name":"Lingbo"},{"first_name":"Abhay","full_name":"Kotecha, Abhay","last_name":"Kotecha"},{"first_name":"Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"}],"title":"Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs","oa_version":"Published Version","volume":214,"date_created":"2022-04-15T07:10:26Z","article_type":"original","oa":1,"language":[{"iso":"eng"}],"citation":{"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>.","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>","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.","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>.","short":"M. Obr, W.J.H. Hagen, R.A. Dick, L. Yu, A. Kotecha, F.K. Schur, Journal of Structural Biology 214 (2022).","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.","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>"},"issue":"2","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"06","department":[{"_id":"FlSc"}],"file":[{"file_id":"11722","file_size":7080863,"date_created":"2022-08-02T11:07:58Z","date_updated":"2022-08-02T11:07:58Z","creator":"dernst","relation":"main_file","checksum":"0b1eb53447aae8e95ae4c12d193b0b00","success":1,"file_name":"2022_JourStructuralBiology_Obr.pdf","access_level":"open_access","content_type":"application/pdf"}],"article_number":"107852"},{"isi":1,"year":"2022","external_id":{"pmid":["35019710"],"isi":["000779305000033"]},"keyword":["virology","insect science","immunology","microbiology"],"publication":"Journal of Virology","status":"public","project":[{"call_identifier":"FWF","name":"Structural conservation and diversity in retroviral capsid","grant_number":"P31445","_id":"26736D6A-B435-11E9-9278-68D0E5697425"}],"pmid":1,"acknowledgement":"This work  was  supported  by  INRAE  starter  funds, Project IDEXLYON  (University  of  Lyon) within  the  Programme  Investissements  d’Avenir  (ANR-16-IDEX-0005),  and  FINOVIAO14 (Fondation  pour  l’Université  de  Lyon),  all  to  P.Y.L.  This  work  was  also  supported  by CellNetworks  Research  Group  funds  and  Deutsche  Forschungsgemeinschaft  (DFG)  funding (grant  numbers  LO-2338/1-1  and  LO-2338/3-1)  awarded  to  P.Y.L., Austrian  Science  Fund (FWF)  grant  P31445  to  F.K.M.S., a  Chinese  Scholarship  Council (CSC;no.  201904910701) fellowship  to   Q.X.,  and  a  ministére  de  l’enseignement  supérieur,  de  la  recherche  et  de l’innovation (MESRI) doctoral thesis grant to M.D.","date_published":"2022-03-01T00:00:00Z","article_processing_charge":"No","doi":"10.1128/jvi.02146-21","publisher":"American Society for Microbiology","_id":"10639","date_updated":"2023-08-02T13:52:33Z","type":"journal_article","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906410"}],"quality_controlled":"1","month":"03","department":[{"_id":"FlSc"}],"article_number":"e02146-21","oa":1,"language":[{"iso":"eng"}],"citation":{"short":"S. Windhaber, Q. Xin, Z.M. Uckeley, J. Koch, M. Obr, C. Garnier, C. Luengo-Guyonnot, M. Duboeuf, F.K. Schur, P.-Y. Lozach, Journal of Virology 96 (2022).","ieee":"S. Windhaber <i>et al.</i>, “The Orthobunyavirus Germiston enters host cells from late endosomes,” <i>Journal of Virology</i>, vol. 96, no. 5. American Society for Microbiology, 2022.","ama":"Windhaber S, Xin Q, Uckeley ZM, et al. The Orthobunyavirus Germiston enters host cells from late endosomes. <i>Journal of Virology</i>. 2022;96(5). doi:<a href=\"https://doi.org/10.1128/jvi.02146-21\">10.1128/jvi.02146-21</a>","mla":"Windhaber, Stefan, et al. “The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes.” <i>Journal of Virology</i>, vol. 96, no. 5, e02146-21, American Society for Microbiology, 2022, doi:<a href=\"https://doi.org/10.1128/jvi.02146-21\">10.1128/jvi.02146-21</a>.","apa":"Windhaber, S., Xin, Q., Uckeley, Z. M., Koch, J., Obr, M., Garnier, C., … Lozach, P.-Y. (2022). The Orthobunyavirus Germiston enters host cells from late endosomes. <i>Journal of Virology</i>. American Society for Microbiology. <a href=\"https://doi.org/10.1128/jvi.02146-21\">https://doi.org/10.1128/jvi.02146-21</a>","chicago":"Windhaber, Stefan, Qilin Xin, Zina M. Uckeley, Jana Koch, Martin Obr, Céline Garnier, Catherine Luengo-Guyonnot, Maëva Duboeuf, Florian KM Schur, and Pierre-Yves Lozach. “The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes.” <i>Journal of Virology</i>. American Society for Microbiology, 2022. <a href=\"https://doi.org/10.1128/jvi.02146-21\">https://doi.org/10.1128/jvi.02146-21</a>.","ista":"Windhaber S, Xin Q, Uckeley ZM, Koch J, Obr M, Garnier C, Luengo-Guyonnot C, Duboeuf M, Schur FK, Lozach P-Y. 2022. The Orthobunyavirus Germiston enters host cells from late endosomes. Journal of Virology. 96(5), e02146-21."},"issue":"5","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","scopus_import":"1","day":"01","author":[{"last_name":"Windhaber","full_name":"Windhaber, Stefan","first_name":"Stefan"},{"first_name":"Qilin","last_name":"Xin","full_name":"Xin, Qilin"},{"full_name":"Uckeley, Zina M.","last_name":"Uckeley","first_name":"Zina M."},{"first_name":"Jana","last_name":"Koch","full_name":"Koch, Jana"},{"first_name":"Martin","full_name":"Obr, Martin","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","last_name":"Obr"},{"first_name":"Céline","full_name":"Garnier, Céline","last_name":"Garnier"},{"first_name":"Catherine","last_name":"Luengo-Guyonnot","full_name":"Luengo-Guyonnot, Catherine"},{"last_name":"Duboeuf","full_name":"Duboeuf, Maëva","first_name":"Maëva"},{"id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian KM","last_name":"Schur","first_name":"Florian KM","orcid":"0000-0003-4790-8078"},{"full_name":"Lozach, Pierre-Yves","last_name":"Lozach","first_name":"Pierre-Yves"}],"title":"The Orthobunyavirus Germiston enters host cells from late endosomes","oa_version":"Published Version","volume":96,"date_created":"2022-01-18T10:04:18Z","article_type":"original","acknowledged_ssus":[{"_id":"EM-Fac"}],"intvolume":"        96","abstract":[{"lang":"eng","text":"With more than 80 members worldwide, the Orthobunyavirus genus in the Peribunyaviridae family is a large genus of enveloped RNA viruses, many of which are emerging pathogens in humans and livestock. How orthobunyaviruses (OBVs) penetrate and infect mammalian host cells remains poorly characterized. Here, we investigated the entry mechanisms of the OBV Germiston (GERV). Viral particles were visualized by cryo-electron microscopy and appeared roughly spherical with an average diameter of 98 nm. Labeling of the virus with fluorescent dyes did not adversely affect its infectivity and allowed the monitoring of single particles in fixed and live cells. Using this approach, we found that endocytic internalization of bound viruses was asynchronous and occurred within 30-40 min. The virus entered Rab5a+ early endosomes and, subsequently, late endosomal vacuoles containing Rab7a but not LAMP-1. Infectious entry did not require proteolytic cleavage, and endosomal acidification was sufficient and necessary for viral fusion. Acid-activated penetration began 15-25 min after initiation of virus internalization and relied on maturation of early endosomes to late endosomes. The optimal pH for viral membrane fusion was slightly below 6.0, and penetration was hampered when the potassium influx was abolished. Overall, our study provides real-time visualization of GERV entry into host cells and demonstrates the importance of late endosomal maturation in facilitating OBV penetration."}],"publication_identifier":{"eissn":["1098-5514"],"issn":["0022-538X"]},"publication_status":"published"},{"article_processing_charge":"No","doi":"10.1038/s41467-021-23506-0","publisher":"Nature Research","_id":"9431","date_updated":"2023-08-08T13:53:53Z","type":"journal_article","ddc":["570"],"quality_controlled":"1","year":"2021","isi":1,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/how-retroviruses-become-infectious/","description":"News on IST Homepage","relation":"press_release"}]},"external_id":{"isi":["000659145000011"]},"keyword":["General Biochemistry","Genetics and Molecular Biology","General Physics and Astronomy","General Chemistry"],"status":"public","publication":"Nature Communications","project":[{"name":"Structural conservation and diversity in retroviral capsid","grant_number":"P31445","call_identifier":"FWF","_id":"26736D6A-B435-11E9-9278-68D0E5697425"}],"acknowledgement":"This work was funded by the National Institute of Allergy and Infectious Diseases under awards R01AI147890 to R.A.D., R01AI150454 to V.M.V, R35GM136258 in support of J-P.R.F, and the Austrian Science Fund (FWF) grant P31445 to F.K.M.S. Access to high-resolution cryo-ET data acquisition at EMBL Heidelberg was supported by iNEXT (grant no. 653706), funded by the Horizon 2020 program of the European Union (PID 4246). We thank Wim Hagen and Felix Weis at EMBL Heidelberg for support in cryo-ET data acquisition. This work made use of the Cornell Center for Materials Research Shared Facilities, which are supported through the NSF MRSEC program (DMR-179875). 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).","date_published":"2021-05-28T00:00:00Z","scopus_import":"1","day":"28","author":[{"first_name":"Martin","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","full_name":"Obr, Martin","last_name":"Obr"},{"full_name":"Ricana, Clifton L.","last_name":"Ricana","first_name":"Clifton L."},{"first_name":"Nadia","full_name":"Nikulin, Nadia","last_name":"Nikulin"},{"first_name":"Jon-Philip R.","full_name":"Feathers, Jon-Philip R.","last_name":"Feathers"},{"full_name":"Klanschnig, Marco","last_name":"Klanschnig","first_name":"Marco"},{"last_name":"Thader","full_name":"Thader, Andreas","id":"3A18A7B8-F248-11E8-B48F-1D18A9856A87","first_name":"Andreas"},{"first_name":"Marc C.","last_name":"Johnson","full_name":"Johnson, Marc C."},{"first_name":"Volker M.","last_name":"Vogt","full_name":"Vogt, Volker M."},{"first_name":"Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian KM"},{"first_name":"Robert A.","full_name":"Dick, Robert A.","last_name":"Dick"}],"oa_version":"Published Version","title":"Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer","volume":12,"date_created":"2021-05-28T14:25:50Z","article_type":"original","has_accepted_license":"1","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"intvolume":"        12","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"text":"Inositol hexakisphosphate (IP6) is an assembly cofactor for HIV-1. We report here that IP6 is also used for assembly of Rous sarcoma virus (RSV), a retrovirus from a different genus. IP6 is ~100-fold more potent at promoting RSV mature capsid protein (CA) assembly than observed for HIV-1 and removal of IP6 in cells reduces infectivity by 100-fold. Here, visualized by cryo-electron tomography and subtomogram averaging, mature capsid-like particles show an IP6-like density in the CA hexamer, coordinated by rings of six lysines and six arginines. Phosphate and IP6 have opposing effects on CA in vitro assembly, inducing formation of T = 1 icosahedrons and tubes, respectively, implying that phosphate promotes pentamer and IP6 hexamer formation. Subtomogram averaging and classification optimized for analysis of pleomorphic retrovirus particles reveal that the heterogeneity of mature RSV CA polyhedrons results from an unexpected, intrinsic CA hexamer flexibility. In contrast, the CA pentamer forms rigid units organizing the local architecture. These different features of hexamers and pentamers determine the structural mechanism to form CA polyhedrons of variable shape in mature RSV particles.","lang":"eng"}],"file_date_updated":"2021-06-09T15:21:14Z","publication_identifier":{"eissn":["2041-1723"]},"publication_status":"published","month":"05","department":[{"_id":"FlSc"}],"file":[{"file_id":"9538","file_size":6166295,"date_created":"2021-06-09T15:21:14Z","creator":"kschuh","date_updated":"2021-06-09T15:21:14Z","relation":"main_file","checksum":"53ccc53d09a9111143839dbe7784e663","file_name":"2021_NatureCommunications_Obr.pdf","success":1,"content_type":"application/pdf","access_level":"open_access"}],"article_number":"3226","oa":1,"language":[{"iso":"eng"}],"citation":{"ama":"Obr M, Ricana CL, Nikulin N, et al. Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23506-0\">10.1038/s41467-021-23506-0</a>","ieee":"M. Obr <i>et al.</i>, “Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer,” <i>Nature Communications</i>, vol. 12, no. 1. Nature Research, 2021.","short":"M. Obr, C.L. Ricana, N. Nikulin, J.-P.R. Feathers, M. Klanschnig, A. Thader, M.C. Johnson, V.M. Vogt, F.K. Schur, R.A. Dick, Nature Communications 12 (2021).","ista":"Obr M, Ricana CL, Nikulin N, Feathers J-PR, Klanschnig M, Thader A, Johnson MC, Vogt VM, Schur FK, Dick RA. 2021. Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer. Nature Communications. 12(1), 3226.","chicago":"Obr, Martin, Clifton L. Ricana, Nadia Nikulin, Jon-Philip R. Feathers, Marco Klanschnig, Andreas Thader, Marc C. Johnson, Volker M. Vogt, Florian KM Schur, and Robert A. Dick. “Structure of the Mature Rous Sarcoma Virus Lattice Reveals a Role for IP6 in the Formation of the Capsid Hexamer.” <i>Nature Communications</i>. Nature Research, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23506-0\">https://doi.org/10.1038/s41467-021-23506-0</a>.","apa":"Obr, M., Ricana, C. L., Nikulin, N., Feathers, J.-P. R., Klanschnig, M., Thader, A., … Dick, R. A. (2021). Structure of the mature Rous sarcoma virus lattice reveals a role for IP6 in the formation of the capsid hexamer. <i>Nature Communications</i>. Nature Research. <a href=\"https://doi.org/10.1038/s41467-021-23506-0\">https://doi.org/10.1038/s41467-021-23506-0</a>","mla":"Obr, Martin, et al. “Structure of the Mature Rous Sarcoma Virus Lattice Reveals a Role for IP6 in the Formation of the Capsid Hexamer.” <i>Nature Communications</i>, vol. 12, no. 1, 3226, Nature Research, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23506-0\">10.1038/s41467-021-23506-0</a>."},"issue":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"external_id":{"isi":["000699841100001"],"pmid":["34578434"]},"isi":1,"year":"2021","keyword":["virology","infectious diseases"],"publication":"Viruses","status":"public","project":[{"call_identifier":"FWF","grant_number":"P31445","name":"Structural conservation and diversity in retroviral capsid","_id":"26736D6A-B435-11E9-9278-68D0E5697425"}],"acknowledgement":"We thank Volker M. Vogt for his critical comments in preparation of the review.","date_published":"2021-09-17T00:00:00Z","pmid":1,"publisher":"MDPI","article_processing_charge":"Yes","doi":"10.3390/v13091853","type":"journal_article","_id":"10103","date_updated":"2023-08-14T07:21:51Z","ddc":["616"],"quality_controlled":"1","month":"09","article_number":"1853","file":[{"relation":"main_file","checksum":"bcfd72a12977d48e22df3d0cc55aacf1","success":1,"file_name":"2021_Viruses_Obr.pdf","access_level":"open_access","content_type":"application/pdf","file_id":"10115","file_size":4146796,"date_created":"2021-10-08T10:38:15Z","date_updated":"2021-10-08T10:38:15Z","creator":"cchlebak"}],"department":[{"_id":"FlSc"}],"language":[{"iso":"eng"}],"oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ieee":"M. Obr, F. K. Schur, and R. A. Dick, “A structural perspective of the role of IP6 in immature and mature retroviral assembly,” <i>Viruses</i>, vol. 13, no. 9. MDPI, 2021.","short":"M. Obr, F.K. Schur, R.A. Dick, Viruses 13 (2021).","ama":"Obr M, Schur FK, Dick RA. A structural perspective of the role of IP6 in immature and mature retroviral assembly. <i>Viruses</i>. 2021;13(9). doi:<a href=\"https://doi.org/10.3390/v13091853\">10.3390/v13091853</a>","apa":"Obr, M., Schur, F. K., &#38; Dick, R. A. (2021). A structural perspective of the role of IP6 in immature and mature retroviral assembly. <i>Viruses</i>. MDPI. <a href=\"https://doi.org/10.3390/v13091853\">https://doi.org/10.3390/v13091853</a>","mla":"Obr, Martin, et al. “A Structural Perspective of the Role of IP6 in Immature and Mature Retroviral Assembly.” <i>Viruses</i>, vol. 13, no. 9, 1853, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/v13091853\">10.3390/v13091853</a>.","ista":"Obr M, Schur FK, Dick RA. 2021. A structural perspective of the role of IP6 in immature and mature retroviral assembly. Viruses. 13(9), 1853.","chicago":"Obr, Martin, Florian KM Schur, and Robert A. Dick. “A Structural Perspective of the Role of IP6 in Immature and Mature Retroviral Assembly.” <i>Viruses</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/v13091853\">https://doi.org/10.3390/v13091853</a>."},"issue":"9","oa_version":"Published Version","title":"A structural perspective of the role of IP6 in immature and mature retroviral assembly","day":"17","author":[{"last_name":"Obr","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","full_name":"Obr, Martin","first_name":"Martin","orcid":"0000-0003-1756-6564"},{"first_name":"Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Dick, Robert A.","last_name":"Dick","first_name":"Robert A."}],"date_created":"2021-10-07T09:13:29Z","article_type":"original","volume":13,"intvolume":"        13","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"lang":"eng","text":"The small cellular molecule inositol hexakisphosphate (IP6) has been known for ~20 years to promote the in vitro assembly of HIV-1 into immature virus-like particles. However, the molecular details underlying this effect have been determined only recently, with the identification of the IP6 binding site in the immature Gag lattice. IP6 also promotes formation of the mature capsid protein (CA) lattice via a second IP6 binding site, and enhances core stability, creating a favorable environment for reverse transcription. IP6 also enhances assembly of other retroviruses, from both the Lentivirus and the Alpharetrovirus genera. These findings suggest that IP6 may have a conserved function throughout the family Retroviridae. Here, we discuss the different steps in the viral life cycle that are influenced by IP6, and describe in detail how IP6 interacts with the immature and mature lattices of different retroviruses."}],"has_accepted_license":"1","file_date_updated":"2021-10-08T10:38:15Z","publication_identifier":{"issn":["1999-4915"]},"publication_status":"published"},{"oa":1,"language":[{"iso":"eng"}],"citation":{"apa":"Turoňová, B., Hagen, W. J. H., Obr, M., Mosalaganti, S., Beugelink, J. W., Zimmerli, C. E., … Beck, M. (2020). Benchmarking tomographic acquisition schemes for high-resolution structural biology. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-020-14535-2\">https://doi.org/10.1038/s41467-020-14535-2</a>","mla":"Turoňová, Beata, et al. “Benchmarking Tomographic Acquisition Schemes for High-Resolution Structural Biology.” <i>Nature Communications</i>, vol. 11, 876, Springer Nature, 2020, doi:<a href=\"https://doi.org/10.1038/s41467-020-14535-2\">10.1038/s41467-020-14535-2</a>.","chicago":"Turoňová, Beata, Wim J.H. Hagen, Martin Obr, Shyamal Mosalaganti, J. Wouter Beugelink, Christian E. Zimmerli, Hans Georg Kräusslich, and Martin Beck. “Benchmarking Tomographic Acquisition Schemes for High-Resolution Structural Biology.” <i>Nature Communications</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41467-020-14535-2\">https://doi.org/10.1038/s41467-020-14535-2</a>.","ista":"Turoňová B, Hagen WJH, Obr M, Mosalaganti S, Beugelink JW, Zimmerli CE, Kräusslich HG, Beck M. 2020. Benchmarking tomographic acquisition schemes for high-resolution structural biology. Nature Communications. 11, 876.","ieee":"B. Turoňová <i>et al.</i>, “Benchmarking tomographic acquisition schemes for high-resolution structural biology,” <i>Nature Communications</i>, vol. 11. Springer Nature, 2020.","short":"B. Turoňová, W.J.H. Hagen, M. Obr, S. Mosalaganti, J.W. Beugelink, C.E. Zimmerli, H.G. Kräusslich, M. Beck, Nature Communications 11 (2020).","ama":"Turoňová B, Hagen WJH, Obr M, et al. Benchmarking tomographic acquisition schemes for high-resolution structural biology. <i>Nature Communications</i>. 2020;11. doi:<a href=\"https://doi.org/10.1038/s41467-020-14535-2\">10.1038/s41467-020-14535-2</a>"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"02","department":[{"_id":"FlSc"}],"article_number":"876","file":[{"file_id":"7517","date_created":"2020-02-24T14:00:54Z","file_size":2027529,"creator":"dernst","date_updated":"2020-07-14T12:47:59Z","relation":"main_file","checksum":"2c8d10475e1b0d397500760e28bdf561","file_name":"2020_NatureComm_Turonova.pdf","content_type":"application/pdf","access_level":"open_access"}],"has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"        11","abstract":[{"text":"Cryo electron tomography with subsequent subtomogram averaging is a powerful technique to structurally analyze macromolecular complexes in their native context. Although close to atomic resolution in principle can be obtained, it is not clear how individual experimental parameters contribute to the attainable resolution. Here, we have used immature HIV-1 lattice as a benchmarking sample to optimize the attainable resolution for subtomogram averaging. We systematically tested various experimental parameters such as the order of projections, different angular increments and the use of the Volta phase plate. We find that although any of the prominently used acquisition schemes is sufficient to obtain subnanometer resolution, dose-symmetric acquisition provides considerably better outcome. We discuss our findings in order to provide guidance for data acquisition. Our data is publicly available and might be used to further develop processing routines.","lang":"eng"}],"publication_identifier":{"eissn":["20411723"]},"publication_status":"published","file_date_updated":"2020-07-14T12:47:59Z","author":[{"first_name":"Beata","full_name":"Turoňová, Beata","last_name":"Turoňová"},{"full_name":"Hagen, Wim J.H.","last_name":"Hagen","first_name":"Wim J.H."},{"first_name":"Martin","orcid":"0000-0003-1756-6564","last_name":"Obr","full_name":"Obr, Martin","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Mosalaganti, Shyamal","last_name":"Mosalaganti","first_name":"Shyamal"},{"full_name":"Beugelink, J. Wouter","last_name":"Beugelink","first_name":"J. Wouter"},{"first_name":"Christian E.","full_name":"Zimmerli, Christian E.","last_name":"Zimmerli"},{"last_name":"Kräusslich","full_name":"Kräusslich, Hans Georg","first_name":"Hans Georg"},{"first_name":"Martin","full_name":"Beck, Martin","last_name":"Beck"}],"scopus_import":"1","day":"13","oa_version":"Published Version","title":"Benchmarking tomographic acquisition schemes for high-resolution structural biology","volume":11,"article_type":"original","date_created":"2020-02-23T23:00:35Z","status":"public","publication":"Nature Communications","date_published":"2020-02-13T00:00:00Z","isi":1,"year":"2020","external_id":{"isi":["000514928000017"]},"ddc":["570"],"quality_controlled":"1","doi":"10.1038/s41467-020-14535-2","article_processing_charge":"No","publisher":"Springer Nature","date_updated":"2023-08-18T06:36:41Z","_id":"7511","type":"journal_article"},{"language":[{"iso":"eng"}],"citation":{"short":"M. Obr, F.K. Schur, in:, F.A. Rey (Ed.), Complementary Strategies to Study Virus Structure and Function, Elsevier, 2019, pp. 117–159.","ieee":"M. Obr and F. K. Schur, “Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging,” in <i>Complementary Strategies to Study Virus Structure and Function</i>, vol. 105, F. A. Rey, Ed. Elsevier, 2019, pp. 117–159.","ama":"Obr M, Schur FK. Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging. In: Rey FA, ed. <i>Complementary Strategies to Study Virus Structure and Function</i>. Vol 105. Advances in Virus Research. Elsevier; 2019:117-159. doi:<a href=\"https://doi.org/10.1016/bs.aivir.2019.07.008\">10.1016/bs.aivir.2019.07.008</a>","mla":"Obr, Martin, and Florian KM Schur. “Structural Analysis of Pleomorphic and Asymmetric Viruses Using Cryo-Electron Tomography and Subtomogram Averaging.” <i>Complementary Strategies to Study Virus Structure and Function</i>, edited by Félix A. Rey, vol. 105, Elsevier, 2019, pp. 117–59, doi:<a href=\"https://doi.org/10.1016/bs.aivir.2019.07.008\">10.1016/bs.aivir.2019.07.008</a>.","apa":"Obr, M., &#38; Schur, F. K. (2019). Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging. In F. A. Rey (Ed.), <i>Complementary Strategies to Study Virus Structure and Function</i> (Vol. 105, pp. 117–159). Elsevier. <a href=\"https://doi.org/10.1016/bs.aivir.2019.07.008\">https://doi.org/10.1016/bs.aivir.2019.07.008</a>","chicago":"Obr, Martin, and Florian KM Schur. “Structural Analysis of Pleomorphic and Asymmetric Viruses Using Cryo-Electron Tomography and Subtomogram Averaging.” In <i>Complementary Strategies to Study Virus Structure and Function</i>, edited by Félix A. Rey, 105:117–59. Advances in Virus Research. Elsevier, 2019. <a href=\"https://doi.org/10.1016/bs.aivir.2019.07.008\">https://doi.org/10.1016/bs.aivir.2019.07.008</a>.","ista":"Obr M, Schur FK. 2019.Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging. In: Complementary Strategies to Study Virus Structure and Function. vol. 105, 117–159."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"08","department":[{"_id":"FlSc"}],"abstract":[{"text":"Describing the protein interactions that form pleomorphic and asymmetric viruses represents a considerable challenge to most structural biology techniques, including X-ray crystallography and single particle cryo-electron microscopy. Obtaining a detailed understanding of these interactions is nevertheless important, considering the number of relevant human pathogens that do not follow strict icosahedral or helical symmetry. Cryo-electron tomography and subtomogram averaging methods provide structural insights into complex biological environments and are well suited to go beyond structures of perfectly symmetric viruses. This chapter discusses recent developments showing that cryo-ET and subtomogram averaging can provide high-resolution insights into hitherto unknown structural features of pleomorphic and asymmetric virus particles. It also describes how these methods have significantly added to our understanding of retrovirus capsid assemblies in immature and mature viruses. Additional examples of irregular viruses and their associated proteins, whose structures have been studied via cryo-ET and subtomogram averaging, further support the versatility of these methods.","lang":"eng"}],"intvolume":"       105","publication_identifier":{"issn":["0065-3527"],"isbn":["9780128184561"]},"publication_status":"published","day":"27","scopus_import":"1","author":[{"last_name":"Obr","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","full_name":"Obr, Martin","first_name":"Martin","orcid":"0000-0003-1756-6564"},{"first_name":"Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"}],"oa_version":"None","title":"Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging","volume":105,"date_created":"2019-09-18T08:15:37Z","publication":"Complementary Strategies to Study Virus Structure and Function","status":"public","pmid":1,"date_published":"2019-08-27T00:00:00Z","year":"2019","isi":1,"external_id":{"pmid":["    31522703"],"isi":["000501594500006"]},"page":"117-159","quality_controlled":"1","article_processing_charge":"No","doi":"10.1016/bs.aivir.2019.07.008","publisher":"Elsevier","editor":[{"first_name":"Félix A.","full_name":"Rey, Félix A.","last_name":"Rey"}],"_id":"6890","date_updated":"2023-08-30T06:56:00Z","series_title":"Advances in Virus Research","type":"book_chapter"},{"acknowledgement":"The authors thank B. Glass for preparation of the immature HIV-1 (D25A) sample; J. Plitzko and D. Tegunov for providing the K2Align software; and S. Mattei, N. Hoffman, F. Thommen, A. Sonnen, and S. Dodonova for technical assistance and/or discussion. This study was supported by Deutsche Forschungsgemeinschaft grants BR 3635/2-1 (to J.A.G.B.) and KR 906/7-1 (to H.-G.K.). The Briggs laboratory acknowledges financial support from the European Molecular Biology Laboratory (EMBL) and from the Chica und Heinz Schaller Stiftung. W.W. was supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 748-2014). A.J.J. acknowledges support by the EMBL Interdisciplinary Postdoc Program under the Marie Curie Action COFUND (PCOFUND-GA-2008-229597) and by the Joachim Herz Stiftung. This study was technically supported by the EMBL information technology services unit and the EMBL Proteomics Core Facility. F.K.M.S., M.O., H.-G.K., and J.A.G.B. designed the experiments, with J.M.K. assisting in the design of those involving mass spectrometry. F.K.M.S. and M.O. prepared samples. W.J.H.H. implemented tomography acquisition schemes. F.K.M.S. and W.J.H.H. acquired the data. F.K.M.S. and W.W. processed images. F.K.M.S., A.J.J., and C.S. refined the model. F.K.M.S., M.O., and J.A.G.B. analyzed the data. F.K.M.S. and J.A.G.B. wrote the manuscript with support from all authors. Representative tomograms and the final electron microscopy structures have been deposited in the Electron Microscopy Data Bank with accession numbers EMD-4015, EMD-4016, EMD-4017, EMD-4018, EMD-4019, and EMD-4020. The refined HIV-1 CA-SP1 model has been deposited in the Protein Data Bank with accession number 5L93.","date_published":"2016-07-29T00:00:00Z","citation":{"ama":"Schur FK, Obr M, Hagen W, et al. An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation. <i>Science</i>. 2016;353(6298):506-508. doi:<a href=\"https://doi.org/10.1126/science.aaf9620\">10.1126/science.aaf9620</a>","short":"F.K. Schur, M. Obr, W. Hagen, W. Wan, A. Jakobi, J. Kirkpatrick, C. Sachse, H. Kraüsslich, J. Briggs, Science 353 (2016) 506–508.","ieee":"F. K. Schur <i>et al.</i>, “An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation,” <i>Science</i>, vol. 353, no. 6298. American Association for the Advancement of Science, pp. 506–508, 2016.","ista":"Schur FK, Obr M, Hagen W, Wan W, Jakobi A, Kirkpatrick J, Sachse C, Kraüsslich H, Briggs J. 2016. An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation. Science. 353(6298), 506–508.","chicago":"Schur, Florian KM, Martin Obr, Wim Hagen, William Wan, Arjen Jakobi, Joanna Kirkpatrick, Carsten Sachse, Hans Kraüsslich, and John Briggs. “An Atomic Model of HIV-1 Capsid-SP1 Reveals Structures Regulating Assembly and Maturation.” <i>Science</i>. American Association for the Advancement of Science, 2016. <a href=\"https://doi.org/10.1126/science.aaf9620\">https://doi.org/10.1126/science.aaf9620</a>.","mla":"Schur, Florian KM, et al. “An Atomic Model of HIV-1 Capsid-SP1 Reveals Structures Regulating Assembly and Maturation.” <i>Science</i>, vol. 353, no. 6298, American Association for the Advancement of Science, 2016, pp. 506–08, doi:<a href=\"https://doi.org/10.1126/science.aaf9620\">10.1126/science.aaf9620</a>.","apa":"Schur, F. K., Obr, M., Hagen, W., Wan, W., Jakobi, A., Kirkpatrick, J., … Briggs, J. (2016). An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.aaf9620\">https://doi.org/10.1126/science.aaf9620</a>"},"issue":"6298","extern":1,"publication":"Science","status":"public","publist_id":"6834","month":"07","year":"2016","publication_status":"published","quality_controlled":0,"abstract":[{"lang":"eng","text":"Immature HIV-1 assembles at and buds from the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation can be blocked by maturation inhibitors (MIs), thereby abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag is the key regulator of assembly and maturation and is the target of MIs.We applied optimized cryo-electron tomography and subtomogram averaging to resolve this region within assembled immature HIV-1 particles at 3.9 angstrom resolution and built an atomic model. The structure reveals a network of intra- And intermolecular interactions mediating immature HIV-1 assembly. The proteolytic cleavage site between CA and SP1 is inaccessible to protease.We suggest that MIs prevent CA-SP1 cleavage by stabilizing the structure, and MI resistance develops by destabilizing CA-SP1."}],"intvolume":"       353","page":"506 - 508","date_created":"2018-12-11T11:48:39Z","type":"journal_article","_id":"816","volume":353,"date_updated":"2021-01-12T08:17:12Z","title":"An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation","publisher":"American Association for the Advancement of Science","day":"29","doi":"10.1126/science.aaf9620","author":[{"first_name":"Florian","orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Florian Schur","last_name":"Schur"},{"first_name":"Martin","last_name":"Obr","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","full_name":"Martin Obr"},{"first_name":"Wim","full_name":"Hagen, Wim J","last_name":"Hagen"},{"first_name":"William","full_name":"Wan, William","last_name":"Wan"},{"last_name":"Jakobi","full_name":"Jakobi, Arjen J","first_name":"Arjen"},{"last_name":"Kirkpatrick","full_name":"Kirkpatrick, Joanna M","first_name":"Joanna"},{"full_name":"Sachse, Carsten","last_name":"Sachse","first_name":"Carsten"},{"last_name":"Kraüsslich","full_name":"Kraüsslich, Hans Georg","first_name":"Hans"},{"last_name":"Briggs","full_name":"Briggs, John A","first_name":"John"}]}]