Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function.

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 ?-? 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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Antibodies, Neutralizing, Antibodies, Viral, Binding Sites, COVID-19, Cryoelectron Microscopy, Humans, Models, Molecular, Mutation, Protein Binding, Protein Domains, Receptors, Virus, SARS-CoV-2, Spike Glycoprotein, Coronavirus
Nat Struct Mol Biol
Date: Sep. 01, 2021
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