气候变化领域集成服务门户(CCPortal): Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion

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DOI	10.1073/pnas.1708727114
	Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion
	Walls A.C.; Tortorici M.A.; Snijder J.; Xiong X.; Bosch B.-J.; Rey F.A.; Veesler D.
发表日期	2017
ISSN	0027-8424
起始页码	11157
结束页码	11162
卷号	114 期号:42
英文摘要	The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. The coronavirus spike (S) glycoprotein initiates infection by promoting fusion of the viral and cellular membranes through conformational changes that remain largely uncharacterized. Here we report the cryoEM structure of a coronavirus S glycoprotein in the postfusion state, showing large-scale secondary, tertiary, and quaternary rearrangements compared with the prefusion trimer and rationalizing the free-energy landscape of this conformational machine. We also biochemically characterized the molecular events associated with refolding of the metastable prefusion S glycoprotein to the postfusion conformation using limited proteolysis, mass spectrometry, and single-particle EM. The observed similarity between postfusion coronavirus S and paramyxovirus F structures demonstrates that a conserved refolding trajectory mediates entry of these viruses and supports the evolutionary relatedness of their fusion subunits. Finally, our data provide a structural framework for understanding the mode of neutralization of antibodies targeting the fusion machinery and for engineering next-generation subunit vaccines or inhibitors against this medically important virus family. © 2017, National Academy of Sciences. All rights reserved.
英文关键词	Coronavirus; CryoEM; Fusion proteins; Membrane fusion; Proteolytic activation
语种	英语
scopus关键词	glycoprotein; Influenza virus hemagglutinin; subunit vaccine; virus fusion protein; vitronectin; coronavirus spike glycoprotein; Article; biochemical analysis; comparative study; conformational transition; controlled study; Coronaviridae; mass spectrometry; membrane fusion; Middle East respiratory syndrome coronavirus; molecular biology; nonhuman; Paramyxoviridae; priority journal; protein analysis; protein degradation; protein refolding; SARS coronavirus; virus morphology; animal; chemistry; cryoelectron microscopy; Drosophila; genetics; HEK293 cell line; human; membrane fusion; metabolism; mutation; protein conformation; validation study; Animals; Cryoelectron Microscopy; Drosophila; HEK293 Cells; Humans; Mass Spectrometry; Membrane Fusion; Mutation; Protein Conformation; Spike Glycoprotein, Coronavirus
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160588
作者单位	Walls, A.C., Department of Biochemistry, University of Washington, Seattle, WA 98195, United States; Tortorici, M.A., Département de Virologie, Unité de Virologie Structurale, Institut Pasteur, Paris, France, CNRS UMR 3569 Virologie, Paris, 75015, France; Snijder, J., Department of Biochemistry, University of Washington, Seattle, WA 98195, United States; Xiong, X., Department of Biochemistry, University of Washington, Seattle, WA 98195, United States; Bosch, B.-J., Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CL, Netherlands; Rey, F.A., Département de Virologie, Unité de Virologie Structurale, Institut Pasteur, Paris, France, CNRS UMR 3569 Virologie, Paris, 75015, France; Veesler, D., Department of Biochemistry, University of Washington, Seattle, WA 98195, United States
推荐引用方式 GB/T 7714	Walls A.C.,Tortorici M.A.,Snijder J.,et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion[J],2017,114(42).
APA	Walls A.C..,Tortorici M.A..,Snijder J..,Xiong X..,Bosch B.-J..,...&Veesler D..(2017).Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion.Proceedings of the National Academy of Sciences of the United States of America,114(42).
MLA	Walls A.C.,et al."Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion".Proceedings of the National Academy of Sciences of the United States of America 114.42(2017).