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Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.

Publication ,  Journal Article
Gobeil, SM-C; Janowska, K; McDowell, S; Mansouri, K; Parks, R; Stalls, V; Kopp, MF; Manne, K; Li, D; Wiehe, K; Saunders, KO; Edwards, RJ ...
Published in: Science
August 6, 2021

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.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

August 6, 2021

Volume

373

Issue

6555

Location

United States

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • SARS-CoV-2
  • Receptors, Coronavirus
  • Protein Subunits
  • Protein Structure, Quaternary
  • Protein Interaction Domains and Motifs
  • Protein Conformation
  • Protein Binding
  • Mutation
  • Models, Molecular
 

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Gobeil, S.-C., Janowska, K., McDowell, S., Mansouri, K., Parks, R., Stalls, V., … Acharya, P. (2021). Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity. Science, 373(6555). https://doi.org/10.1126/science.abi6226
Gobeil, Sophie M-C, Katarzyna Janowska, Shana McDowell, Katayoun Mansouri, Robert Parks, Victoria Stalls, Megan F. Kopp, et al. “Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.Science 373, no. 6555 (August 6, 2021). https://doi.org/10.1126/science.abi6226.
Gobeil SM-C, Janowska K, McDowell S, Mansouri K, Parks R, Stalls V, et al. Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity. Science. 2021 Aug 6;373(6555).
Gobeil, Sophie M. C., et al. “Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity.Science, vol. 373, no. 6555, Aug. 2021. Pubmed, doi:10.1126/science.abi6226.
Gobeil SM-C, Janowska K, McDowell S, Mansouri K, Parks R, Stalls V, Kopp MF, Manne K, Li D, Wiehe K, Saunders KO, Edwards RJ, Korber B, Haynes BF, Henderson R, Acharya P. Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity. Science. 2021 Aug 6;373(6555).
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

August 6, 2021

Volume

373

Issue

6555

Location

United States

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • SARS-CoV-2
  • Receptors, Coronavirus
  • Protein Subunits
  • Protein Structure, Quaternary
  • Protein Interaction Domains and Motifs
  • Protein Conformation
  • Protein Binding
  • Mutation
  • Models, Molecular