7YP2

Cryo-EM structure of EBV gHgL-gp42 in complex with mAb 6H2 (localized refinement)

7YP2 の概要

• エントリーDOI: 10.2210/pdb7yp2/pdb
• EMDBエントリー: 33994
• 分子名称: Envelope glycoprotein H, 6H2 heavy chain, 6H2 light chain (3 entities in total)
• 機能のキーワード: ebv, cryo-em, glycoprotein, ghgl-gp42 complex, antibody, viral protein
• 由来する生物種: Human gammaherpesvirus 4 (Epstein-Barr virus); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 60330.30

構造登録者

Liu, L.,Sun, H.,Jiang, Y.,Hong, J.,Zheng, Q.,Li, S.,Chen, Y.,Xia, N. (登録日: 2022-08-02, 公開日: 2024-01-31, 最終更新日: 2024-11-13)

主引用文献

Hong, J.,Zhong, L.,Liu, L.,Wu, Q.,Zhang, W.,Chen, K.,Wei, D.,Sun, H.,Zhou, X.,Zhang, X.,Kang, Y.F.,Huang, Y.,Chen, J.,Wang, G.,Zhou, Y.,Chen, Y.,Feng, Q.S.,Yu, H.,Li, S.,Zeng, M.S.,Zeng, Y.X.,Xu, M.,Zheng, Q.,Chen, Y.,Zhang, X.,Xia, N.
Non-overlapping epitopes on the gHgL-gp42 complex for the rational design of a triple-antibody cocktail against EBV infection.
Cell Rep Med, 4:101296-101296, 2023

PubMed Abstract: Epstein-Barr virus (EBV) is closely associated with cancer, multiple sclerosis, and post-acute coronavirus disease 2019 (COVID-19) sequelae. There are currently no approved therapeutics or vaccines against EBV. It is noteworthy that combining multiple EBV glycoproteins can elicit potent neutralizing antibodies (nAbs) against viral infection, suggesting possible synergistic effects. Here, we characterize three nAbs (anti-gp42 5E3, anti-gHgL 6H2, and anti-gHgL 10E4) targeting different glycoproteins of the gHgL-gp42 complex. Two antibody cocktails synergistically neutralize infection in B cells (5E3+6H2+10E4) and epithelial cells (6H2+10E4) in vitro. Moreover, 5E3 alone and the 5E3+6H2+10E4 cocktail confer potent in vivo protection against lethal EBV challenge in humanized mice. The cryo-EM structure of a heptatomic gHgL-gp42 immune complex reveals non-overlapping epitopes of 5E3, 6H2, and 10E4 on the gHgL-gp42 complex. Structural and functional analyses highlight different neutralization mechanisms for each of the three nAbs. In summary, our results provide insight for the rational design of therapeutics or vaccines against EBV infection.

PubMed: 37992686
DOI: 10.1016/j.xcrm.2023.101296

実験手法

ELECTRON MICROSCOPY (3.52 Å)