tetano
Editor, Senior Moderator
Cell Rep
. 2023 Jan 4;42(1):111964.
doi: 10.1016/j.celrep.2022.111964. Online ahead of print.
Structural analysis of receptor engagement and antigenic drift within the BA.2 spike protein
James W Saville[SUP] 1 [/SUP], Dhiraj Mannar[SUP] 1 [/SUP], Xing Zhu[SUP] 1 [/SUP], Alison M Berezuk[SUP] 1 [/SUP], Spencer Cholak[SUP] 1 [/SUP], Katherine S Tuttle[SUP] 1 [/SUP], Faezeh Vahdatihassani[SUP] 1 [/SUP], Sriram Subramaniam[SUP] 2 [/SUP]
Affiliations
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 β-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.
Keywords: COVID-19; CP: Immunology; CP: Molecular biology; Omicron; SARS-CoV-2; cryoelectron microscopy.
. 2023 Jan 4;42(1):111964.
doi: 10.1016/j.celrep.2022.111964. Online ahead of print.
Structural analysis of receptor engagement and antigenic drift within the BA.2 spike protein
James W Saville[SUP] 1 [/SUP], Dhiraj Mannar[SUP] 1 [/SUP], Xing Zhu[SUP] 1 [/SUP], Alison M Berezuk[SUP] 1 [/SUP], Spencer Cholak[SUP] 1 [/SUP], Katherine S Tuttle[SUP] 1 [/SUP], Faezeh Vahdatihassani[SUP] 1 [/SUP], Sriram Subramaniam[SUP] 2 [/SUP]
Affiliations
- PMID: 36640338
- DOI: 10.1016/j.celrep.2022.111964
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 β-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.
Keywords: COVID-19; CP: Immunology; CP: Molecular biology; Omicron; SARS-CoV-2; cryoelectron microscopy.