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Basic Characteristics of Mutations
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Mutation Site
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A570D |
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Mutation Site Sentence
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The B.1.1.7-specific A570D mutation introduces a molecular switch that could modulate the opening and closing of the RBD. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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B.1.1.7 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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COVID-19
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Immune
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Y |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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UK |
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Literature Information
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PMID
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34385690
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Title
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Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function
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Author
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Yang TJ,Yu PY,Chang YC,Liang KH,Tso HC,Ho MR,Chen WY,Lin HT,Wu HC,Hsu SD
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Journal
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Nature structural & molecular biology
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Journal Info
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2021 Sep;28(9):731-739
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Abstract
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The B.1.1.7 variant of SARS-CoV-2 first detected in the UK harbors amino-acid substitutions and deletions in the spike protein that potentially enhance host angiotensin conversion enzyme 2 (ACE2) receptor binding and viral immune evasion. Here we report cryo-EM structures of the spike protein of B.1.1.7 in the apo and ACE2-bound forms. The apo form showed one or two receptor-binding domains (RBDs) in the open conformation, without populating the fully closed state. All three RBDs were engaged in ACE2 binding. The B.1.1.7-specific A570D mutation introduces a molecular switch that could modulate the opening and closing of the RBD. The N501Y mutation introduces a pi-pi interaction that enhances RBD binding to ACE2 and abolishes binding of a potent neutralizing antibody (nAb). Cryo-EM also revealed how a cocktail of two nAbs simultaneously bind to all three RBDs, and demonstrated the potency of the nAb cocktail to neutralize different SARS-CoV-2 pseudovirus strains, including B.1.1.7.
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Sequence Data
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-
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