7L7R

CCHFV Gc prefusion monomer bound to ADI-36121 and ADI-37801 Fabs

7L7R の概要

• エントリーDOI: 10.2210/pdb7l7r/pdb
• 分子名称: ADI-36121 Fab light chain, ADI-36121 Fab heavy chain, ADI-37801 Fab light chain, ... (7 entities in total)
• 機能のキーワード: fusion protein, antibody, fab complex, class ii fusion, viral protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 158077.45

構造登録者

Mishra, A.K.,McLellan, J.S. (登録日: 2020-12-30, 公開日: 2021-12-01, 最終更新日: 2024-11-13)

主引用文献

Mishra, A.K.,Hellert, J.,Freitas, N.,Guardado-Calvo, P.,Haouz, A.,Fels, J.M.,Maurer, D.P.,Abelson, D.M.,Bornholdt, Z.A.,Walker, L.M.,Chandran, K.,Cosset, F.L.,McLellan, J.S.,Rey, F.A.
Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies.
Science, 375:104-109, 2022

PubMed Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-borne zoonotic virus, with a 30% case fatality rate in humans. Structural information is lacking in regard to the CCHFV membrane fusion glycoprotein Gc—the main target of the host neutralizing antibody response—as well as antibody–mediated neutralization mechanisms. We describe the structure of prefusion Gc bound to the antigen-binding fragments (Fabs) of two neutralizing antibodies that display synergy when combined, as well as the structure of trimeric, postfusion Gc. The structures show the two Fabs acting in concert to block membrane fusion, with one targeting the fusion loops and the other blocking Gc trimer formation. The structures also revealed the neutralization mechanism of previously reported antibodies against CCHFV, providing the molecular underpinnings essential for developing CCHFV–specific medical countermeasures for epidemic preparedness.

PubMed: 34793197
DOI: 10.1126/science.abl6502

実験手法

X-RAY DIFFRACTION (2.1 Å)