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-Structure paper
Title | Structural analysis of receptor engagement and antigenic drift within the BA.2 spike protein. |
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Journal, issue, pages | Cell Rep, Vol. 42, Issue 1, Page 111964, Year 2023 |
Publish date | Jan 4, 2023 |
Authors | James W Saville / Dhiraj Mannar / Xing Zhu / Alison M Berezuk / Spencer Cholak / Katharine S Tuttle / Faezeh Vahdatihassani / Sriram Subramaniam / |
PubMed 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 ...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. |
External links | Cell Rep / PubMed:36640338 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.37 - 3.04 Å |
Structure data | EMDB-27523, PDB-8dm1: EMDB-27524, PDB-8dm2: EMDB-27525, PDB-8dm3: EMDB-27526, PDB-8dm4: EMDB-27527, PDB-8dm5: EMDB-27528, PDB-8dm6: EMDB-27529, PDB-8dm7: EMDB-27530, PDB-8dm8: EMDB-27531, PDB-8dm9: EMDB-27532, PDB-8dma: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN / SARS-CoV-2 / glycoprotein / fusion protein / Omicron / BA.2 / NTD / VIRAL PROTEIN/IMMUNE SYSTEM / Viral Protein-Immune System complex / 4A8 / ACE2 / mouse / BA.1 |