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Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies.

<div class='caption-title'>Structure of the SARS-CoV-2 N501Y mutant spike protein ectodomain bound to the ACE2 ectodomain.</div>
<div class='caption-title'>Analysis of VH Fc ab8 and IgG ab1 interactions with N501Y and unmutated spike.</div>
<div class='caption-title'>Structure of VH ab8 bound to the N501Y mutant spike protein trimer.</div>
Zhu X, Mannar D, Srivastava SS, Berezuk AM, Demers JP, Saville JW, Leopold K, Li W, Dimitrov DS, Tuttle KS, Zhou S, Chittori S, Subramaniam S
OpenAccess logo PLoS Biol 19 e3001237 (2021)
Related entries: 7mjh, 7mji, 7mjj, 7mjk, 7mjl, 7mjm, 7mjn

Cited: 121 times
EuropePMC logo PMID: 33914735

Abstract

The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments.

Articles - 7mjg mentioned but not cited (9)

  1. Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. Zhu X, Mannar D, Srivastava SS, Berezuk AM, Demers JP, Saville JW, Leopold K, Li W, Dimitrov DS, Tuttle KS, Zhou S, Chittori S, Subramaniam S. PLoS Biol 19 e3001237 (2021)
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Reviews citing this publication (32)

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