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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 Zhu, Xing; Mannar, Dhiraj; Srivastava, Shanti Swaroop; Berezuk, Alison; Demers, Jean-Philippe; Saville, James; Leopold, Karoline; Li, Wei; Dimitrov, Dimiter S.; Tuttle, Katharine; et al.

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.

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Title
Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies
Creator
Zhu, Xing; Mannar, Dhiraj; Srivastava, Shanti Swaroop; Berezuk, Alison; Demers, Jean-Philippe; Saville, James; Leopold, Karoline; Li, Wei; Dimitrov, Dimiter S.; Tuttle, Katharine; Zhou, Steven; Chittori, Sagar; Subramaniam, Sriram
Publisher
PLoS Biology
Date Issued
2021-04-29
Description
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.
Genre
Article
Type
Text
Language
eng
Date Available
2021-06-09
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International
DOI
10.14288/1.0398312
URI
http://hdl.handle.net/2429/78566
Affiliation
Medicine, Faculty of; Non UBC; Biochemistry and Molecular Biology, Department of
Citation
Zhu, X., Mannar, D., Srivastava, S. S., Berezuk, A. M., Demers, J., Saville, J. W., Leopold, K., Li, W., Dimitrov, D. S., Tuttle, K. S., Zhou, S., Chittori, S., & Subramaniam, S. (2021). Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. PLoS Biology, 19(4), e3001237-e3001237.
Publisher DOI
10.1371/journal.pbio.3001237
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher; Postdoctoral; Graduate
Copyright Holder
Authors
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International