7ECY

EV-D68 in complex with 2H12 Fab (State 3)

7ECY の概要

• エントリーDOI: 10.2210/pdb7ecy/pdb
• EMDBエントリー: 31060
• 分子名称: Capsid protein VP1, Capsid protein VP3, Capsid protein VP2, ... (5 entities in total)
• 機能のキーワード: enterovirus d68, monoclonal antibody, uncoating, virus
• 由来する生物種: Human enterovirus D68 (EV68, EV-68); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 134173.91

構造登録者

Xu, C.,Cong, Y. (登録日: 2021-03-13, 公開日: 2021-03-31, 最終更新日: 2024-10-30)

主引用文献

Zhang, C.,Xu, C.,Dai, W.,Wang, Y.,Liu, Z.,Zhang, X.,Wang, X.,Wang, H.,Gong, S.,Cong, Y.,Huang, Z.
Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections.
Nat Commun, 12:2904-2904, 2021

PubMed Abstract: Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), show distinct preference in binding VLP and virion and in neutralizing different EV-D68 strains. A combination of 2H12 and 8F12 exhibits balanced and potent neutralization effects and confers broader protection in mice than single MAbs when given at onset of symptoms. Cryo-EM structures of EV-D68 virion complexed with 2H12 or 8F12 show that both antibodies bind to the canyon region of the virion, creating steric hindrance for sialic acid receptor binding. Additionally, 2H12 binding can impair virion integrity and trigger premature viral uncoating. We also capture an uncoating intermediate induced by 2H12 binding, not previously described for picornaviruses. Our study elucidates the structural basis and neutralizing mechanisms of the 2H12 and 8F12 MAbs and supports further development of the 2H12/8F12 cocktail as a broad-spectrum therapeutic agent against EV-D68 infections in humans.

PubMed: 34006855
DOI: 10.1038/s41467-021-23199-5

実験手法

ELECTRON MICROSCOPY (3.6 Å)