6VY5

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

Summary for 6VY5

• Entry DOI: 10.2210/pdb6vy5/pdb
• Descriptor: 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)
• Functional Keywords: henipavirus, hendra virus, receptor binding protein, antibody, antibody-antigen complex, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 97185.03

Authors

Dong, J.,Crowe, J.E. (deposition date: 2020-02-25, release date: 2021-01-06, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.4 Å)