6DZM

Bundibugyo virus GP (mucin-deleted) in complex with pan-ebolavirus human antibody ADI-15878 Fab

6DZM の概要

• エントリーDOI: 10.2210/pdb6dzm/pdb
• EMDBエントリー: 8936
• 分子名称: Bundibugyo virus GP1, Bundibugyo virus GP2, Antibody ADI-15878 Fab, light chain, ... (7 entities in total)
• 機能のキーワード: antibody, pan-ebolavirus, internal fusion loop, hr1, glycoprotein, viral protein
• 由来する生物種: Bundibugyo ebolavirus; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 241609.54

構造登録者

Murin, C.D.,Ward, A.B. (登録日: 2018-07-05, 公開日: 2018-09-12, 最終更新日: 2020-07-29)

主引用文献

Murin, C.D.,Bruhn, J.F.,Bornholdt, Z.A.,Copps, J.,Stanfield, R.,Ward, A.B.
Structural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the Glycoprotein Fusion Loop.
Cell Rep, 24:2723-2732.e4, 2018

PubMed Abstract: Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack of a molecular understanding of cross-reactive epitopes. The antibody ADI-15878 was previously identified from a human survivor of Ebola virus Makona variant (EBOV/Mak) infection. This mAb demonstrated potent neutralizing activity against all known ebolaviruses and provided protection in rodent and ferret models against three ebolavirus species. Here, we describe the unliganded crystal structure of ADI-15878 as well as the cryo-EM structures of ADI-15878 in complex with the EBOV/Mak and Bundibugyo virus (BDBV) glycoproteins (GPs). ADI-15878 binds through an induced-fit mechanism by targeting highly conserved residues in the internal fusion loop (IFL), bridging across GP protomers via the heptad repeat 1 (HR1) region. Our structures provide a more complete description of the ebolavirus immunogenic landscape, as well as a molecular basis for how rare but potent antibodies target conserved filoviral fusion machinery.

PubMed: 30184505
DOI: 10.1016/j.celrep.2018.08.009

実験手法

ELECTRON MICROSCOPY (4.29 Å)