6N7J

BDBV223 Fab bound to synthetic peptide of Bundibugyo virus Glycoprotein Stalk

6N7J の概要

• エントリーDOI: 10.2210/pdb6n7j/pdb
• 分子名称: BDBV223 antibody heavy chain, BDBV223 antibody light chain, Envelope glycoprotein (3 entities in total)
• 機能のキーワード: antibody, antiviral protein, 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: 6
• 化学式量合計: 100628.70

構造登録者

King, L.B.,West, B.R.,Saphire, E.O. (登録日: 2018-11-27, 公開日: 2019-03-20, 最終更新日: 2024-10-16)

主引用文献

King, L.B.,West, B.R.,Moyer, C.L.,Gilchuk, P.,Flyak, A.,Ilinykh, P.A.,Bombardi, R.,Hui, S.,Huang, K.,Bukreyev, A.,Crowe Jr., J.E.,Saphire, E.O.
Cross-reactive neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk.
Nat Commun, 10:1788-1788, 2019

PubMed Abstract: Three Ebolavirus genus viruses cause lethal disease and lack targeted therapeutics: Ebola virus, Sudan virus and Bundibugyo virus. Monoclonal antibody (mAb) cocktails against the surface glycoprotein (GP) present a potential therapeutic strategy. Here we report two crystal structures of the antibody BDBV223, alone and complexed with its GP2 stalk epitope, an interesting site for therapeutic/vaccine design due to its high sequence conservation among ebolaviruses. BDBV223, identified in a human survivor of Bundibugyo virus disease, neutralizes both Bundibugyo virus and Ebola virus, but not Sudan virus. Importantly, the structure suggests that BDBV223 binding interferes with both the trimeric bundle assembly of GP and the viral membrane by stabilizing a conformation in which the monomers are separated by GP lifting or bending. Targeted mutagenesis of BDBV223 to enhance SUDV GP recognition indicates that additional determinants of antibody binding likely lie outside the visualized interactions, and perhaps involve quaternary assembly or membrane-interacting regions.

PubMed: 30996276
DOI: 10.1038/s41467-019-09732-7

実験手法

X-RAY DIFFRACTION (3.684 Å)