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...
Main Authors: | , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2020-10-01
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Series: | Cell Reports |
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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. |
first_indexed | 2024-12-12T05:36:43Z |
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institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-12-12T05:36:43Z |
publishDate | 2020-10-01 |
publisher | Elsevier |
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series | Cell Reports |
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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