气候变化领域集成服务门户(CCPortal): Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity

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DOI	10.1126/science.abi6226
	Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity
	Gobeil S.M.-C.; Janowska K.; McDowell S.; Mansouri K.; Parks R.; Stalls V.; Kopp M.F.; Manne K.; Li D.; Wiehe K.; Saunders K.O.; Edwards R.J.; Korber B.; Haynes B.F.; Henderson R.; Acharya P.
发表日期	2021
ISSN	0036-8075
卷号	373 期号:6555
英文摘要	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike mutations enable increased transmission and antibody resistance. We combined cryo-electron microscopy (cryo-EM), binding, and computational analyses to study variant spikes, including one that was involved in transmission between minks and humans, and others that originated and spread in human populations. All variants showed increased angiotensin-converting enzyme 2 (ACE2) receptor binding and increased propensity for receptor binding domain (RBD)-up states. While adaptation to mink resulted in spike destabilization, the B.1.1.7 (UK) spike balanced stabilizing and destabilizing mutations. A local destabilizing effect of the RBD E484K mutation was implicated in resistance of the B.1.1.28/P.1 (Brazil) and B.1.351 (South Africa) variants to neutralizing antibodies. Our studies revealed allosteric effects of mutations and mechanistic differences that drive either interspecies transmission or escape from antibody neutralization. © 2021 American Association for the Advancement of Science. All rights reserved.
英文关键词	angiotensin converting enzyme 2; coronavirus spike glycoprotein; neutralizing antibody; potassium channel KCNE1; ACE2 protein, human; coronavirus spike glycoprotein; neutralizing antibody; protein binding; spike protein, SARS-CoV-2; virus antibody; virus antigen; antibiotic resistance; antibiotics; antibody; chemical binding; detection method; enzyme; enzyme activity; mutation; neutralization; severe acute respiratory syndrome; allosterism; antigenicity; Article; Brazil; cryoelectron microscopy; Neovison vison; nonhuman; protein conformation; protein structure; receptor binding; SARS-CoV-2 variant 501Y.V2; Severe acute respiratory syndrome coronavirus 2; South Africa; virus mutation; virus transmission; amino acid substitution; animal; chemistry; genetics; human; immune evasion; immunology; metabolism; molecular model; mutation; protein conformation; protein domain; protein quaternary structure; protein subunit; veterinary medicine; virology; Brazil; South Africa; Elliptio dilatata; SARS coronavirus; Amino Acid Substitution; Angiotensin-Converting Enzyme 2; Animals; Antibodies, Neutralizing; Antibodies, Viral; Antigens, Viral; COVID-19; Cryoelectron Microscopy; Host Adaptation; Humans; Immune Evasion; Mink; Models, Molecular; Mutation; Protein Binding; Protein Conformation; Protein Interaction Domains and Motifs; Protein Structure, Quaternary; Protein Subunits; Receptors, Coronavirus; SARS-CoV-2; Spike Glycoprotein, Coronavirus
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/243821
作者单位	Duke Human Vaccine Institute, Durham, NC 27710, United States; Department of Medicine, Duke University, Durham, NC 27710, United States; Department of Surgery, Duke University, Durham, NC 27710, United States; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, United States; Department of Immunology, Duke University, Durham, NC 27710, United States; Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, United States; Department of Biochemistry, Duke University, Durham, NC 27710, United States
推荐引用方式 GB/T 7714	Gobeil S.M.-C.,Janowska K.,McDowell S.,et al. Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity[J],2021,373(6555).
APA	Gobeil S.M.-C..,Janowska K..,McDowell S..,Mansouri K..,Parks R..,...&Acharya P..(2021).Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.Science,373(6555).
MLA	Gobeil S.M.-C.,et al."Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity".Science 373.6555(2021).