Cell Reports
Volume 33, Issue 3, 20 October 2020, 108274
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Article
An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain

https://doi.org/10.1016/j.celrep.2020.108274Get rights and content
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Highlights

  • Crystal structures of IGHV3-53 antibodies that frequently bind SARS-CoV-2 RBD

  • Binding modes (A and B) of these IGHV3-53 antibodies depend on CDR H3 length

  • Germline-encoded CDR H1 and H2 motifs dominate the two binding poses

  • CDR H3 length of IGHV3-53 antibodies is associated with light chain preference

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.

Keywords

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

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These authors contributed equally

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