9RDH

Structure of A16/G9 in complex with A56/K2 at pH 5.5 (vaccinia virus)

9RDH の概要

• エントリーDOI: 10.2210/pdb9rdh/pdb
• EMDBエントリー: 53936
• 分子名称: Virion membrane protein OPG143, Entry-fusion complex protein OPG094, Superinfection exclusion protein, ... (7 entities in total)
• 機能のキーワード: poxvirus, viral fusion, vaccinia virus, mpox virus, viral protein
• 由来する生物種: Vaccinia virus Western Reserve; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 138764.37

構造登録者

Vernuccio, R.,Battini, L.,Meola, A.,Guardado-Calvo, P. (登録日: 2025-06-02, 公開日: 2025-09-03, 最終更新日: 2025-09-10)

主引用文献

Meola, A.,Vernuccio, R.,Battini, L.,Albericio, G.,Delgado, P.,Bamford, R.,Pokorny, L.,Broutin, M.,Martinez Leon, A.,Gallien, S.,Gil, M.,Noriega, M.A.,Guivel-Benhassine, F.,Porrot, F.,Postal, J.,Buchrieser, J.,Hubert, M.,Haouz, A.,Lafaye, P.,Esteban, M.,Hub, J.S.,Mahevas, M.,Chappert, P.,Mercer, J.,Garcia-Arriaza, J.,Schwartz, O.,Guardado-Calvo, P.
Structural basis of poxvirus fusion regulation and anti-A16/G9 antibody-mediated neutralization and protection.
Cell, 2025

PubMed Abstract: Monkeypox virus (MPXV) is a poxvirus endemic to Central and West Africa with high epidemic potential. Poxviruses enter host cells via a conserved entry-fusion complex (EFC), which mediates viral fusion to the cell membrane. The EFC is a promising therapeutic target, but the absence of structural data has limited the development of fusion-inhibiting treatments. Here, we investigated A16/G9, a subcomplex of the EFC that controls fusion timing. Using cryo-electron microscopy, we showed how A16/G9 interacts with A56/K2, a viral fusion suppressor that prevents superinfection. Immunization with A16/G9 elicited a protective immune response in mice. Using X-ray crystallography, we characterized two neutralizing antibodies and engineered a chimeric antibody that cross-neutralizes several poxviruses more efficiently than 7D11, the most potent antibody targeting the EFC described to date. These findings highlight the potential of A16/G9 as a candidate for subunit vaccines and identify regions of the EFC as targets for antiviral development.

PubMed: 40865523
DOI: 10.1016/j.cell.2025.07.040

実験手法

ELECTRON MICROSCOPY (4 Å)