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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2020-10-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720312638
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author 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
author_facet 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
author_sort Nicholas C. Wu
collection DOAJ
description 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.
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spelling doaj.art-6bf6b5594a8547aba5c424f38aad6fb72022-12-22T00:36:07ZengElsevierCell Reports2211-12472020-10-01333108274An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding DomainNicholas C. Wu0Meng Yuan1Hejun Liu2Chang-Chun D. Lee3Xueyong Zhu4Sandhya Bangaru5Jonathan L. Torres6Tom G. Caniels7Philip J.M. Brouwer8Marit J. van Gils9Rogier W. Sanders10Andrew B. Ward11Ian A. Wilson12Department 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, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute, 1105AZ Amsterdam, the NetherlandsDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute, 1105AZ Amsterdam, the NetherlandsDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection and Immunity Institute, 1105AZ Amsterdam, the NetherlandsDepartment 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, USADepartment 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, USADepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720312638COVID-19SARS-CoV-2antibodiesx-ray crystallographyspike proteinreceptor-binding domain
spellingShingle 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
An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain
Cell Reports
COVID-19
SARS-CoV-2
antibodies
x-ray crystallography
spike protein
receptor-binding domain
title An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain
title_full An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain
title_fullStr An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain
title_full_unstemmed An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain
title_short An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain
title_sort alternative binding mode of ighv3 53 antibodies to the sars cov 2 receptor binding domain
topic COVID-19
SARS-CoV-2
antibodies
x-ray crystallography
spike protein
receptor-binding domain
url http://www.sciencedirect.com/science/article/pii/S2211124720312638
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