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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number108274
JournalCell Reports
Issue number3
StatePublished - Oct 20 2020


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

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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