An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain

Nicholas C. Wu; Meng Yuan; Hejun Liu; Chang-Chun D. Lee; Xueyong Zhu; Sandhya Bangaru; Jonathan L. Torres; Tom G. Caniels; Philip J. M. Brouwer; Marit J. van Gils; Rogier W. Sanders; Andrew B. Ward; Ian A. Wilson

doi:https://doi.org/10.1016/j.celrep.2020.108274

An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain

Nicholas C. Wu, Meng Yuan, Hejun Liu, Chang-Chun D. Lee, Xueyong Zhu, Sandhya Bangaru, Jonathan L. Torres, Tom G. Caniels, Philip J. M. Brouwer, Marit J. van Gils, Rogier W. Sanders, Andrew B. Ward, Ian A. Wilson

Research output: Contribution to journal › Article › Academic › peer-review

105 Citations (Scopus)

Abstract

IGHV3-53-encoded neutralizing antibodies are commonly elicited during SARS-CoV-2 infection and target the receptor-binding domain (RBD) of the spike (S) protein. Such IGHV3-53 antibodies generally have a short CDR H3 because of structural constraints in binding the RBD (mode A). However, a small subset of IGHV3-53 antibodies to the RBD contain a longer CDR H3. Crystal structures of two IGHV3-53 neutralizing antibodies here demonstrate that a longer CDR H3 can be accommodated in a different binding mode (mode B). These two classes of IGHV3-53 antibodies both target the ACE2 receptor binding site, but with very different angles of approach and molecular interactions. Overall, these findings emphasize the versatility of IGHV3-53 in this common antibody response to SARS-CoV-2, where conserved IGHV3-53 germline-encoded features can be combined with very different CDR H3 lengths and light chains for SARS-CoV-2 RBD recognition and virus neutralization.

Original language	English
Article number	108274
Journal	Cell reports
Volume	33
Issue number	3
Early online date	2020
DOIs	https://doi.org/10.1016/j.celrep.2020.108274
Publication status	Published - 20 Oct 2020

Keywords

COVID-19
SARS-CoV-2
antibodies
receptor-binding domain
spike protein
x-ray crystallography

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title = "An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain",

abstract = "IGHV3-53-encoded neutralizing antibodies are commonly elicited during SARS-CoV-2 infection and target the receptor-binding domain (RBD) of the spike (S) protein. Such IGHV3-53 antibodies generally have a short CDR H3 because of structural constraints in binding the RBD (mode A). However, a small subset of IGHV3-53 antibodies to the RBD contain a longer CDR H3. Crystal structures of two IGHV3-53 neutralizing antibodies here demonstrate that a longer CDR H3 can be accommodated in a different binding mode (mode B). These two classes of IGHV3-53 antibodies both target the ACE2 receptor binding site, but with very different angles of approach and molecular interactions. Overall, these findings emphasize the versatility of IGHV3-53 in this common antibody response to SARS-CoV-2, where conserved IGHV3-53 germline-encoded features can be combined with very different CDR H3 lengths and light chains for SARS-CoV-2 RBD recognition and virus neutralization.",

keywords = "COVID-19, SARS-CoV-2, antibodies, receptor-binding domain, spike protein, x-ray crystallography",

author = "Wu, {Nicholas C.} and Meng Yuan and Hejun Liu and Lee, {Chang-Chun D.} and Xueyong Zhu and Sandhya Bangaru and Torres, {Jonathan L.} and Caniels, {Tom G.} and Brouwer, {Philip J. M.} and {van Gils}, {Marit J.} and Sanders, {Rogier W.} and Ward, {Andrew B.} and Wilson, {Ian A.}",

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AU - Zhu, Xueyong

AU - Bangaru, Sandhya

AU - Torres, Jonathan L.

AU - Caniels, Tom G.

AU - Brouwer, Philip J. M.

AU - van Gils, Marit J.

AU - Sanders, Rogier W.

AU - Ward, Andrew B.

AU - Wilson, Ian A.

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AB - IGHV3-53-encoded neutralizing antibodies are commonly elicited during SARS-CoV-2 infection and target the receptor-binding domain (RBD) of the spike (S) protein. Such IGHV3-53 antibodies generally have a short CDR H3 because of structural constraints in binding the RBD (mode A). However, a small subset of IGHV3-53 antibodies to the RBD contain a longer CDR H3. Crystal structures of two IGHV3-53 neutralizing antibodies here demonstrate that a longer CDR H3 can be accommodated in a different binding mode (mode B). These two classes of IGHV3-53 antibodies both target the ACE2 receptor binding site, but with very different angles of approach and molecular interactions. Overall, these findings emphasize the versatility of IGHV3-53 in this common antibody response to SARS-CoV-2, where conserved IGHV3-53 germline-encoded features can be combined with very different CDR H3 lengths and light chains for SARS-CoV-2 RBD recognition and virus neutralization.

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An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain

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Keywords

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