globalchange  > 气候变化与战略
DOI: 10.1073/pnas.1708727114
论文题名:
Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion
作者: Walls A.C.; Tortorici M.A.; Snijder J.; Xiong X.; Bosch B.-J.; Rey F.A.; Veesler D.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2017
卷: 114, 期:42
起始页码: 11157
结束页码: 11162
语种: 英语
英文关键词: Coronavirus ; CryoEM ; Fusion proteins ; Membrane fusion ; Proteolytic activation
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
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.
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163787
Appears in Collections:气候变化与战略

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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

Recommended Citation:
Walls A.C.,Tortorici M.A.,Snijder J.,et al. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion[J]. Proceedings of the National Academy of Sciences of the United States of America,2017-01-01,114(42)
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