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

Cell Reports (Oct 2020)

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

Affiliations

Nicholas C. Wu: Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
Meng Yuan: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Hejun Liu: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Chang-Chun D. Lee: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Xueyong Zhu: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Sandhya Bangaru: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Jonathan L. Torres: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Tom G. Caniels: Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute, 1105AZ Amsterdam, the Netherlands
Philip J.M. Brouwer: Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute, 1105AZ Amsterdam, the Netherlands
Marit J. van Gils: Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute, 1105AZ Amsterdam, the Netherlands
Rogier W. Sanders: Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute, 1105AZ Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA
Andrew B. Ward: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
Ian A. Wilson: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA; Corresponding author

Journal volume & issue: Vol. 33, no. 3
p. 108274

Abstract

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Summary: 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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