8A1E

Rabies virus glycoprotein in complex with Fab fragments of 17C7 and 1112-1 neutralizing antibodies

8A1E の概要

• エントリーDOI: 10.2210/pdb8a1e/pdb
• EMDBエントリー: 15073
• 分子名称: Glycoprotein, Fab 17C7 heavy chain variable domain, Fab 17C7 light chain variable domain, ... (5 entities in total)
• 機能のキーワード: viral glycoprotein, antibody, complex, viral protein
• 由来する生物種: Rabies virus strain Pasteur vaccin; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 106571.37

構造登録者

Ng, W.M.,Fedosyuk, S.,English, S.,Augusto, G.,Berg, A.,Thorley, L.,Haselon, A.S.,Segireddy, R.R.,Bowden, T.A.,Douglas, A.D. (登録日: 2022-06-01, 公開日: 2022-08-17, 最終更新日: 2024-11-06)

主引用文献

Ng, W.M.,Fedosyuk, S.,English, S.,Augusto, G.,Berg, A.,Thorley, L.,Haselon, A.S.,Segireddy, R.R.,Bowden, T.A.,Douglas, A.D.
Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies.
Cell Host Microbe, 30:1219-1230.e7, 2022

PubMed Abstract: Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host-cell entry. RABV-G's pre-fusion trimeric conformation displays epitopes bound by protective neutralizing antibodies that can be induced by vaccination or passively administered for post-exposure prophylaxis. We report a 2.8-Å structure of a RABV-G trimer in the pre-fusion conformation, in complex with two neutralizing and protective monoclonal antibodies, 17C7 and 1112-1, that recognize distinct epitopes. One of these antibodies is a licensed prophylactic (17C7, Rabishield), which we show locks the protein in pre-fusion conformation. Targeted mutations can similarly stabilize RABV-G in the pre-fusion conformation, a key step toward structure-guided vaccine design. These data reveal the higher-order architecture of a key therapeutic target and the structural basis of neutralization by antibodies binding two key antigenic sites, and this will facilitate the development of improved vaccines and prophylactic antibodies.

PubMed: 35985336
DOI: 10.1016/j.chom.2022.07.014

実験手法

ELECTRON MICROSCOPY (2.83 Å)