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. Graphical Abstract 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 Antibodies to the SARS-CoV-2 receptor-binding domain are commonly encoded by IGHV3-53, and most have a short CDR H3. Wu et al. show that IGHV3-53 antibodies with a long CDR H3 adopt an alternative binding mode, demonstrating that IGHV3-53 is even more versatile than previously thought in targeting SARS-CoV-2.
【저자키워드】 COVID-19, antibodies, SARS-CoV-2, X-ray crystallography, Spike protein, Receptor-binding domain, 【초록키워드】 neutralizing antibody, antibody, SARS-COV-2 infection, Antibody Response, Protein, RBD, Virus neutralization, molecular, crystal structure, IGHV3-53, interactions, binding, SARS-CoV-2 RBD, domain, motif, approach, feature, CDR H3, thought, ACE2 receptor binding, conserved, the RBD, the receptor-binding domain, elicited, subset, CDR H1, the SARS-CoV-2, 【제목키워드】 IGHV3-53, mode, the SARS-CoV-2,