8DM8

Cryo-EM structure of SARS-CoV-2 Omicron BA.2 spike protein in complex with mouse ACE2 (focused refinement of RBD and ACE2)

8DM8 の概要

• エントリーDOI: 10.2210/pdb8dm8/pdb
• EMDBエントリー: 27530
• 分子名称: Spike glycoprotein, Angiotensin-converting enzyme 2, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: sars-cov-2, glycoprotein, fusion protein, viral protein, viral protein-immune system complex, omicron, ba.2, mouse, ace2
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 214900.96

構造登録者

Zhu, X.,Saville, J.W.,Mannar, D.,Berezuk, A.M.,Cholak, S.,Tuttle, K.S.,Vahdatihassani, F.,Subramaniam, S. (登録日: 2022-07-08, 公開日: 2023-02-08, 最終更新日: 2024-10-16)

主引用文献

Saville, J.W.,Mannar, D.,Zhu, X.,Berezuk, A.M.,Cholak, S.,Tuttle, K.S.,Vahdatihassani, F.,Subramaniam, S.
Structural analysis of receptor engagement and antigenic drift within the BA.2 spike protein.
Cell Rep, 42:111964-111964, 2023

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 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.

PubMed: 36640338
DOI: 10.1016/j.celrep.2022.111964

実験手法

ELECTRON MICROSCOPY (2.68 Å)