8WE1

SARS-CoV-2 Omicron BF.7 RBD complexed with human ACE2

8WE1 の概要

• エントリーDOI: 10.2210/pdb8we1/pdb
• EMDBエントリー: 37470
• 分子名称: Angiotensin-converting enzyme 2, Spike protein S2', 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: rbd, viral protein, virus
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 119922.64

構造登録者

Li, W.,Xie, Y. (登録日: 2023-09-16, 公開日: 2024-07-24, 最終更新日: 2025-07-02)

主引用文献

Li, W.,Xu, Z.,Niu, T.,Xie, Y.,Zhao, Z.,Li, D.,He, Q.,Sun, W.,Shi, K.,Guo, W.,Chang, Z.,Liu, K.,Fan, Z.,Qi, J.,Gao, G.F.
Key mechanistic features of the trade-off between antibody escape and host cell binding in the SARS-CoV-2 Omicron variant spike proteins.
Embo J., 43:1484-1498, 2024

PubMed Abstract: Since SARS-CoV-2 Omicron variant emerged, it is constantly evolving into multiple sub-variants, including BF.7, BQ.1, BQ.1.1, XBB, XBB.1.5 and the recently emerged BA.2.86 and JN.1. Receptor binding and immune evasion are recognized as two major drivers for evolution of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the underlying mechanism of interplay between two factors remains incompletely understood. Herein, we determined the structures of human ACE2 complexed with BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5 RBDs. Based on the ACE2/RBD structures of these sub-variants and a comparison with the known complex structures, we found that R346T substitution in the RBD enhanced ACE2 binding upon an interaction with the residue R493, but not Q493, via a mechanism involving long-range conformation changes. Furthermore, we found that R493Q and F486V exert a balanced impact, through which immune evasion capability was somewhat compromised to achieve an optimal receptor binding. We propose a "two-steps-forward and one-step-backward" model to describe such a compromise between receptor binding affinity and immune evasion during RBD evolution of Omicron sub-variants.

PubMed: 38467833
DOI: 10.1038/s44318-024-00062-z

実験手法

ELECTRON MICROSCOPY (2.47 Å)