6MAM

Cleaved Ebola GP in complex with a broadly neutralizing human antibody, ADI-15946

6MAM の概要

• エントリーDOI: 10.2210/pdb6mam/pdb
• 分子名称: ADI-15946 Fab Heavy Chain, ADI-15946 Fab Light Chain, Envelope glycoprotein, ... (6 entities in total)
• 機能のキーワード: ebola, ebolavirus, antibody, mab, fab, gp, glycoprotein, cleaved, monoclonal, broad, filovirus, marburg, ebov, bdbv, sudv, restv, tafv, marv, ravv, bundibugyo, sudan, human, viral 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: 12
• 化学式量合計: 264472.51

構造登録者

West, B.R.,Moyer, C.L.,Fusco, M.L.,Saphire, E.O. (登録日: 2018-08-28, 公開日: 2019-03-20, 最終更新日: 2024-11-20)

主引用文献

West, B.R.,Wec, A.Z.,Moyer, C.L.,Fusco, M.L.,Ilinykh, P.A.,Huang, K.,Wirchnianski, A.S.,James, R.M.,Herbert, A.S.,Hui, S.,Goodwin, E.,Howell, K.A.,Kailasan, S.,Aman, M.J.,Walker, L.M.,Dye, J.M.,Bukreyev, A.,Chandran, K.,Saphire, E.O.
Structural basis of broad ebolavirus neutralization by a human survivor antibody.
Nat. Struct. Mol. Biol., 26:204-212, 2019

PubMed Abstract: The structural features that govern broad-spectrum activity of broadly neutralizing anti-ebolavirus antibodies (Abs) outside of the internal fusion loop epitope are currently unknown. Here we describe the structure of a broadly neutralizing human monoclonal Ab (mAb), ADI-15946, which was identified in a human survivor of the 2013-2016 outbreak. The crystal structure of ADI-15946 in complex with cleaved Ebola virus glycoprotein (EBOV GP) reveals that binding of the mAb structurally mimics the conserved interaction between the EBOV GP core and its glycan cap β17-β18 loop to inhibit infection. Both endosomal proteolysis of EBOV GP and binding of mAb FVM09 displace this loop, thereby increasing exposure of ADI-15946's conserved epitope and enhancing neutralization. Our work also mapped the paratope of ADI-15946, thereby explaining reduced activity against Sudan virus, which enabled rational, structure-guided engineering to enhance binding and neutralization of Sudan virus while retaining the parental activity against EBOV and Bundibugyo virus.

PubMed: 30833785
DOI: 10.1038/s41594-019-0191-4

実験手法

X-RAY DIFFRACTION (4.1 Å)