7V26

XG005-bound SARS-CoV-2 S

7V26 の概要

• エントリーDOI: 10.2210/pdb7v26/pdb
• EMDBエントリー: 31637 31638
• 分子名称: Spike glycoprotein, XG005 Heavy chain, XG005 Light Chain, ... (4 entities in total)
• 機能のキーワード: sars-coc-2, spike, antibodies, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 579547.30

構造登録者

Zhan, W.Q.,Zhang, X.,Sun, L.,Chen, Z.G. (登録日: 2021-08-07, 公開日: 2021-10-20, 最終更新日: 2025-07-02)

主引用文献

Liu, Z.,Xu, W.,Chen, Z.,Fu, W.,Zhan, W.,Gao, Y.,Zhou, J.,Zhou, Y.,Wu, J.,Wang, Q.,Zhang, X.,Hao, A.,Wu, W.,Zhang, Q.,Li, Y.,Fan, K.,Chen, R.,Jiang, Q.,Mayer, C.T.,Schoofs, T.,Xie, Y.,Jiang, S.,Wen, Y.,Yuan, Z.,Wang, K.,Lu, L.,Sun, L.,Wang, Q.
An ultrapotent pan-beta-coronavirus lineage B ( beta-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.
Protein Cell, 13:655-675, 2022

PubMed Abstract: New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.

PubMed: 34554412
DOI: 10.1007/s13238-021-00871-6

実験手法

ELECTRON MICROSCOPY (3.85 Å)