8YGU

Cryo-EM structure of simian rotavirus SA11 VP4 in complex with nAb 7H13-I54G mutant (right side)

8YGU の概要

• エントリーDOI: 10.2210/pdb8ygu/pdb
• EMDBエントリー: 39264
• 分子名称: Outer capsid protein VP4, Antibody 7H13-I54G mutant heavy chain, Antibody 7H13-I54G mutant light chain, ... (4 entities in total)
• 機能のキーワード: virus, rotavirus, vp4, 7h13
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 263507.47

構造登録者

Huang, Y.,Sun, H.,Zheng, Q.,Li, S.,Ge, S.,Xia, N. (登録日: 2024-02-27, 公開日: 2025-02-12)

主引用文献

Huang, Y.,Song, F.,Zeng, Y.,Sun, H.,Sheng, R.,Wang, X.,Liu, L.,Luo, G.,Jiang, Y.,Chen, Y.,Zhang, M.,Zhang, S.,Gu, Y.,Yu, H.,Li, S.,Li, T.,Zheng, Q.,Ge, S.,Zhang, J.,Xia, N.
A single residue switch mediates the broad neutralization of Rotaviruses.
Nat Commun, 16:838-838, 2025

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) could offer escape-tolerant and lasting protection against viral infections and therefore guide development of broad-spectrum vaccines. The increasing challenge posed by viral evolution and immune evasion intensifies the importance of the discovery of bNAbs and their underlying neutralization mechanism. Here, focusing on the pivotal viral protein VP4 of rotavirus (RV), we identify a potent bNAb, 7H13, exhibiting broad-spectrum neutralization across diverse RV genotypes and demonstrating strong prevention of virus infection in female mice. A combination of time-resolved cryo-electron microscopy (cryo-EM) and in situ cryo-electron tomography (cryo-ET) analysis reveals a counterintuitive dynamic process of virus inactivation, in which 7H13 asymmetrically binds to a conserved epitope in the capsid-proximal aspect of VP4, triggers a conformational switch in a critical residue-F418-thereby disrupts the meta-stable conformation of VP4 essential for normal viral infection. Structure-guided mutagenesis corroborates the essential role of the 7H13 heavy chain I54 in activating F418 switch and destabilizing VP4. These findings define an atypical NAbs' neutralization mechanism and reveal a potential type of virus vulnerable site for universal vaccine and therapeutics design.

PubMed: 39833145
DOI: 10.1038/s41467-025-56114-3

実験手法

ELECTRON MICROSCOPY (3.13 Å)