[{"date_published":"2020-11-01T00:00:00Z","publisher":"Springer Nature","volume":27,"quality_controlled":"1","page":"1077-1085","department":[{"_id":"LeSa"}],"abstract":[{"lang":"eng","text":"The majority of adenosine triphosphate (ATP) powering cellular processes in eukaryotes is produced by the mitochondrial F1Fo ATP synthase. Here, we present the atomic models of the membrane Fo domain and the entire mammalian (ovine) F1Fo, determined by cryo-electron microscopy. Subunits in the membrane domain are arranged in the ‘proton translocation cluster’ attached to the c-ring and a more distant ‘hook apparatus’ holding subunit e. Unexpectedly, this subunit is anchored to a lipid ‘plug’ capping the c-ring. We present a detailed proton translocation pathway in mammalian Fo and key inter-monomer contacts in F1Fo multimers. Cryo-EM maps of F1Fo exposed to calcium reveal a retracted subunit e and a disassembled c-ring, suggesting permeability transition pore opening. We propose a model for the permeability transition pore opening, whereby subunit e pulls the lipid plug out of the c-ring. Our structure will allow the design of drugs for many emerging applications in medicine."}],"external_id":{"isi":["000569299400004"],"pmid":["32929284"]},"publication_status":"published","doi":"10.1038/s41594-020-0503-8","_id":"8581","article_type":"original","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"ScienComp"}],"related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/structure-of-atpase-solved/","relation":"press_release"}]},"year":"2020","acknowledgement":"We thank J. Novacek from CEITEC (Brno, Czech Republic) for assistance with collecting the FEI Krios dataset and iNEXT for providing access to CEITEC. We thank the IST Austria EM facility for access and assistance with collecting the FEI Glacios dataset. Data processing was performed at the IST high-performance computing cluster. This work has been supported by iNEXT EM HEDC (proposal 4506), funded by the Horizon 2020 Programme of the European Commission.","date_created":"2020-09-28T08:59:27Z","citation":{"apa":"Pinke, G., Zhou, L., &#38; Sazanov, L. A. (2020). Cryo-EM structure of the entire mammalian F-type ATP synthase. <i>Nature Structural and Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-020-0503-8\">https://doi.org/10.1038/s41594-020-0503-8</a>","mla":"Pinke, Gergely, et al. “Cryo-EM Structure of the Entire Mammalian F-Type ATP Synthase.” <i>Nature Structural and Molecular Biology</i>, vol. 27, no. 11, Springer Nature, 2020, pp. 1077–85, doi:<a href=\"https://doi.org/10.1038/s41594-020-0503-8\">10.1038/s41594-020-0503-8</a>.","chicago":"Pinke, Gergely, Long Zhou, and Leonid A Sazanov. “Cryo-EM Structure of the Entire Mammalian F-Type ATP Synthase.” <i>Nature Structural and Molecular Biology</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41594-020-0503-8\">https://doi.org/10.1038/s41594-020-0503-8</a>.","ista":"Pinke G, Zhou L, Sazanov LA. 2020. Cryo-EM structure of the entire mammalian F-type ATP synthase. Nature Structural and Molecular Biology. 27(11), 1077–1085.","short":"G. Pinke, L. Zhou, L.A. Sazanov, Nature Structural and Molecular Biology 27 (2020) 1077–1085.","ieee":"G. Pinke, L. Zhou, and L. A. Sazanov, “Cryo-EM structure of the entire mammalian F-type ATP synthase,” <i>Nature Structural and Molecular Biology</i>, vol. 27, no. 11. Springer Nature, pp. 1077–1085, 2020.","ama":"Pinke G, Zhou L, Sazanov LA. Cryo-EM structure of the entire mammalian F-type ATP synthase. <i>Nature Structural and Molecular Biology</i>. 2020;27(11):1077-1085. doi:<a href=\"https://doi.org/10.1038/s41594-020-0503-8\">10.1038/s41594-020-0503-8</a>"},"type":"journal_article","status":"public","pmid":1,"publication_identifier":{"issn":["15459993"],"eissn":["15459985"]},"month":"11","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"None","day":"01","author":[{"full_name":"Pinke, Gergely","first_name":"Gergely","id":"4D5303E6-F248-11E8-B48F-1D18A9856A87","last_name":"Pinke"},{"first_name":"Long","full_name":"Zhou, Long","id":"3E751364-F248-11E8-B48F-1D18A9856A87","last_name":"Zhou","orcid":"0000-0002-1864-8951"},{"first_name":"Leonid A","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov"}],"publication":"Nature Structural and Molecular Biology","language":[{"iso":"eng"}],"isi":1,"scopus_import":"1","intvolume":"        27","issue":"11","article_processing_charge":"No","date_updated":"2023-08-22T09:33:09Z","title":"Cryo-EM structure of the entire mammalian F-type ATP synthase"},{"publication":"Science","language":[{"iso":"eng"}],"intvolume":"       365","scopus_import":"1","isi":1,"title":"Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase","issue":"6455","article_processing_charge":"No","date_updated":"2023-08-29T07:52:02Z","type":"journal_article","status":"public","pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"None","day":"23","publication_identifier":{"issn":["0036-8075"],"eissn":["1095-9203"]},"month":"08","author":[{"id":"3E751364-F248-11E8-B48F-1D18A9856A87","last_name":"Zhou","orcid":"0000-0002-1864-8951","full_name":"Zhou, Long","first_name":"Long"},{"first_name":"Leonid A","full_name":"Sazanov, Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","orcid":"0000-0002-0977-7989"}],"doi":"10.1126/science.aaw9144","acknowledged_ssus":[{"_id":"ScienComp"}],"_id":"6859","related_material":{"link":[{"relation":"press_release","description":"News on IST Website","url":"https://ist.ac.at/en/news/structure-of-protein-nano-turbine-revealed/"}]},"article_number":"eaaw9144","date_created":"2019-09-07T19:04:45Z","citation":{"apa":"Zhou, L., &#38; Sazanov, L. A. (2019). Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase. <i>Science</i>. AAAS. <a href=\"https://doi.org/10.1126/science.aaw9144\">https://doi.org/10.1126/science.aaw9144</a>","short":"L. Zhou, L.A. Sazanov, Science 365 (2019).","ieee":"L. Zhou and L. A. Sazanov, “Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase,” <i>Science</i>, vol. 365, no. 6455. AAAS, 2019.","ama":"Zhou L, Sazanov LA. Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase. <i>Science</i>. 2019;365(6455). doi:<a href=\"https://doi.org/10.1126/science.aaw9144\">10.1126/science.aaw9144</a>","chicago":"Zhou, Long, and Leonid A Sazanov. “Structure and Conformational Plasticity of the Intact Thermus Thermophilus V/A-Type ATPase.” <i>Science</i>. AAAS, 2019. <a href=\"https://doi.org/10.1126/science.aaw9144\">https://doi.org/10.1126/science.aaw9144</a>.","ista":"Zhou L, Sazanov LA. 2019. Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase. Science. 365(6455), eaaw9144.","mla":"Zhou, Long, and Leonid A. Sazanov. “Structure and Conformational Plasticity of the Intact Thermus Thermophilus V/A-Type ATPase.” <i>Science</i>, vol. 365, no. 6455, eaaw9144, AAAS, 2019, doi:<a href=\"https://doi.org/10.1126/science.aaw9144\">10.1126/science.aaw9144</a>."},"year":"2019","volume":365,"quality_controlled":"1","department":[{"_id":"LeSa"}],"date_published":"2019-08-23T00:00:00Z","publisher":"AAAS","abstract":[{"lang":"eng","text":"V (vacuolar)/A (archaeal)-type adenosine triphosphatases (ATPases), found in archaeaand eubacteria, couple ATP hydrolysis or synthesis to proton translocation across theplasma membrane using the rotary-catalysis mechanism. They belong to the V-typeATPase family, which differs from the mitochondrial/chloroplast F-type ATP synthasesin overall architecture. We solved cryo–electron microscopy structures of the intactThermus thermophilusV/A-ATPase, reconstituted into lipid nanodiscs, in three rotationalstates and two substates. These structures indicate substantial flexibility betweenV1and Voin a working enzyme, which results from mechanical competition between centralshaft rotation and resistance from the peripheral stalks. We also describedetails of adenosine diphosphate inhibition release, V1-Votorque transmission, andproton translocation, which are relevant for the entire V-type ATPase family."}],"external_id":{"isi":["000482464000043"],"pmid":["31439765"]},"publication_status":"published"},{"status":"public","type":"journal_article","date_published":"2015-11-02T00:00:00Z","pmid":1,"publisher":"American Society of Hematology","quality_controlled":"1","volume":127,"page":"529-537","extern":"1","publication_identifier":{"issn":["0006-4971","1528-0020"]},"month":"11","abstract":[{"lang":"eng","text":"The osteoclast-associated receptor (OSCAR) is a collagen-binding immune receptor with important roles in dendritic cell maturation and activation of inflammatory monocytes as well as in osteoclastogenesis. The crystal structure of the OSCAR ectodomain is presented, both free and in complex with a consensus triple-helical peptide (THP). The structures revealed a collagen-binding site in each immunoglobulin-like domain (D1 and D2). The THP binds near a predicted collagen-binding groove in D1, but a more extensive interaction with D2 is facilitated by the unusually wide D1-D2 interdomain angle in OSCAR. Direct binding assays, combined with site-directed mutagenesis, confirm that the primary collagen-binding site in OSCAR resides in D2, in marked contrast to the related collagen receptors, glycoprotein VI (GPVI) and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). Monomeric OSCAR D1D2 binds to the consensus THP with a KD of 28 µM measured in solution, but shows a higher affinity (KD 1.5 μM) when binding to a solid-phase THP, most likely due to an avidity effect. These data suggest a 2-stage model for the interaction of OSCAR with a collagen fibril, with transient, low-affinity interactions initiated by the membrane-distal D1, followed by firm adhesion to the primary binding site in D2."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["26552697"]},"oa_version":"None","day":"02","publication_status":"published","author":[{"last_name":"Zhou","id":"3E751364-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1864-8951","full_name":"Zhou, Long","first_name":"Long"},{"last_name":"Hinerman","full_name":"Hinerman, J. M.","first_name":"J. M."},{"full_name":"Blaszczyk, M.","first_name":"M.","last_name":"Blaszczyk"},{"first_name":"J. L. C.","full_name":"Miller, J. L. C.","last_name":"Miller"},{"first_name":"D. G.","full_name":"Conrady, D. G.","last_name":"Conrady"},{"last_name":"Barrow","first_name":"A. D.","full_name":"Barrow, A. D."},{"first_name":"D. Y.","full_name":"Chirgadze, D. Y.","last_name":"Chirgadze"},{"last_name":"Bihan","first_name":"D.","full_name":"Bihan, D."},{"last_name":"Farndale","first_name":"R. W.","full_name":"Farndale, R. W."},{"last_name":"Herr","full_name":"Herr, A. B.","first_name":"A. B."}],"publication":"Blood","doi":"10.1182/blood-2015-08-667055","language":[{"iso":"eng"}],"_id":"6507","intvolume":"       127","issue":"5","year":"2015","date_updated":"2021-01-12T08:07:47Z","citation":{"mla":"Zhou, Long, et al. “Structural Basis for Collagen Recognition by the Immune Receptor OSCAR.” <i>Blood</i>, vol. 127, no. 5, American Society of Hematology, 2015, pp. 529–37, doi:<a href=\"https://doi.org/10.1182/blood-2015-08-667055\">10.1182/blood-2015-08-667055</a>.","ista":"Zhou L, Hinerman JM, Blaszczyk M, Miller JLC, Conrady DG, Barrow AD, Chirgadze DY, Bihan D, Farndale RW, Herr AB. 2015. Structural basis for collagen recognition by the immune receptor OSCAR. Blood. 127(5), 529–537.","chicago":"Zhou, Long, J. M. Hinerman, M. Blaszczyk, J. L. C. Miller, D. G. Conrady, A. D. Barrow, D. Y. Chirgadze, D. Bihan, R. W. Farndale, and A. B. Herr. “Structural Basis for Collagen Recognition by the Immune Receptor OSCAR.” <i>Blood</i>. American Society of Hematology, 2015. <a href=\"https://doi.org/10.1182/blood-2015-08-667055\">https://doi.org/10.1182/blood-2015-08-667055</a>.","ama":"Zhou L, Hinerman JM, Blaszczyk M, et al. Structural basis for collagen recognition by the immune receptor OSCAR. <i>Blood</i>. 2015;127(5):529-537. doi:<a href=\"https://doi.org/10.1182/blood-2015-08-667055\">10.1182/blood-2015-08-667055</a>","ieee":"L. Zhou <i>et al.</i>, “Structural basis for collagen recognition by the immune receptor OSCAR,” <i>Blood</i>, vol. 127, no. 5. American Society of Hematology, pp. 529–537, 2015.","short":"L. Zhou, J.M. Hinerman, M. Blaszczyk, J.L.C. Miller, D.G. Conrady, A.D. Barrow, D.Y. Chirgadze, D. Bihan, R.W. Farndale, A.B. Herr, Blood 127 (2015) 529–537.","apa":"Zhou, L., Hinerman, J. M., Blaszczyk, M., Miller, J. L. C., Conrady, D. G., Barrow, A. D., … Herr, A. B. (2015). Structural basis for collagen recognition by the immune receptor OSCAR. <i>Blood</i>. American Society of Hematology. <a href=\"https://doi.org/10.1182/blood-2015-08-667055\">https://doi.org/10.1182/blood-2015-08-667055</a>"},"date_created":"2019-05-31T09:38:50Z","title":"Structural basis for collagen recognition by the immune receptor OSCAR"}]