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An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain
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 sub...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522650/ https://www.ncbi.nlm.nih.gov/pubmed/33027617 http://dx.doi.org/10.1016/j.celrep.2020.108274 |
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author | Wu, Nicholas C. Yuan, Meng Liu, Hejun Lee, Chang-Chun D. Zhu, Xueyong Bangaru, Sandhya Torres, Jonathan L. Caniels, Tom G. Brouwer, Philip J.M. van Gils, Marit J. Sanders, Rogier W. Ward, Andrew B. Wilson, Ian A. |
author_facet | Wu, Nicholas C. Yuan, Meng Liu, Hejun Lee, Chang-Chun D. Zhu, Xueyong Bangaru, Sandhya Torres, Jonathan L. Caniels, Tom G. Brouwer, Philip J.M. van Gils, Marit J. Sanders, Rogier W. Ward, Andrew B. Wilson, Ian A. |
author_sort | Wu, Nicholas C. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7522650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-75226502020-09-29 An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain Wu, Nicholas C. Yuan, Meng Liu, Hejun Lee, Chang-Chun D. Zhu, Xueyong Bangaru, Sandhya Torres, Jonathan L. Caniels, Tom G. Brouwer, Philip J.M. van Gils, Marit J. Sanders, Rogier W. Ward, Andrew B. Wilson, Ian A. Cell Rep Article 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. Cell Press 2020-09-29 /pmc/articles/PMC7522650/ /pubmed/33027617 http://dx.doi.org/10.1016/j.celrep.2020.108274 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wu, Nicholas C. Yuan, Meng Liu, Hejun Lee, Chang-Chun D. Zhu, Xueyong Bangaru, Sandhya Torres, Jonathan L. Caniels, Tom G. Brouwer, Philip J.M. van Gils, Marit J. Sanders, Rogier W. Ward, Andrew B. Wilson, Ian A. An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522650/ https://www.ncbi.nlm.nih.gov/pubmed/33027617 http://dx.doi.org/10.1016/j.celrep.2020.108274 |
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