6VY5

Crystal structure of Nipah receptor binding protein head domain in complex with human neutralizing antibody HENV-26

6VY5 の概要

• エントリーDOI: 10.2210/pdb6vy5/pdb
• 分子名称: Anti-Hendra receptor binding protein antibody HENV-26 Fab heavy chain, Anti-Hendra receptor binding protein antibody HENV-26 Fab light chain, receptor binding protein, ... (4 entities in total)
• 機能のキーワード: henipavirus, hendra virus, receptor binding protein, antibody, antibody-antigen complex, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 97185.03

構造登録者

Dong, J.,Crowe, J.E. (登録日: 2020-02-25, 公開日: 2021-01-06, 最終更新日: 2024-10-30)

主引用文献

Dong, J.,Cross, R.W.,Doyle, M.P.,Kose, N.,Mousa, J.J.,Annand, E.J.,Borisevich, V.,Agans, K.N.,Sutton, R.,Nargi, R.,Majedi, M.,Fenton, K.A.,Reichard, W.,Bombardi, R.G.,Geisbert, T.W.,Crowe Jr., J.E.
Potent Henipavirus Neutralization by Antibodies Recognizing Diverse Sites on Hendra and Nipah Virus Receptor Binding Protein.
Cell, 183:1536-1550.e17, 2020

PubMed Abstract: Hendra (HeV) and Nipah (NiV) viruses are emerging zoonotic pathogens in the Henipavirus genus causing outbreaks of disease with very high case fatality rates. Here, we report the first naturally occurring human monoclonal antibodies (mAbs) against HeV receptor binding protein (RBP). All isolated mAbs neutralized HeV, and some also neutralized NiV. Epitope binning experiments identified five major antigenic sites on HeV-RBP. Animal studies demonstrated that the most potent cross-reactive neutralizing mAbs, HENV-26 and HENV-32, protected ferrets in lethal models of infection with NiV Bangladesh 3 days after exposure. We solved the crystal structures of mAb HENV-26 in complex with both HeV-RBP and NiV-RBP and of mAb HENV-32 in complex with HeV-RBP. The studies reveal diverse sites of vulnerability on RBP recognized by potent human mAbs that inhibit virus by multiple mechanisms. These studies identify promising prophylactic antibodies and define protective epitopes that can be used in rational vaccine design.

PubMed: 33306954
DOI: 10.1016/j.cell.2020.11.023

実験手法

X-RAY DIFFRACTION (3.4 Å)