Structural analysis of receptor engagement and antigenic drift within the BA.2 spike protein.
Cell Rep
; 42(1): 111964, 2023 01 31.
Article
en En
| MEDLINE
| ID: mdl-36640338
ABSTRACT
The BA.2 sub-lineage of the Omicron (B.1.1.529) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant rapidly supplanted the original BA.1 sub-lineage in early 2022. Both lineages threatened the efficacy of vaccine-elicited antibodies and acquired increased binding to several mammalian ACE2 receptors. Cryoelectron microscopy (cryo-EM) analysis of the BA.2 spike (S) glycoprotein in complex with mouse ACE2 (mACE2) identifies BA.1- and BA.2-mutated residues Q493R, N501Y, and Y505H as complementing non-conserved residues between human and mouse ACE2, rationalizing the enhanced S protein-mACE2 interaction for Omicron variants. Cryo-EM structures of the BA.2 S-human ACE2 complex and of the extensively mutated BA.2 amino-terminal domain (NTD) reveal a dramatic reorganization of the highly antigenic N1 loop into a ß-strand, providing an explanation for decreased binding of the BA.2 S protein to antibodies isolated from BA.1-convalescent patients. Our analysis reveals structural mechanisms underlying the antigenic drift in the rapidly evolving Omicron variant landscape.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
COVID-19
/
Deriva y Cambio Antigénico
Límite:
Animals
/
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article