8X99

Cryo-EM structure of coxsackievirus A16 A-particle in complex with Fab h1A6.2

8X99 の概要

• エントリーDOI: 10.2210/pdb8x99/pdb
• EMDBエントリー: 38169
• 分子名称: Capsid protein VP1, Capsid protein VP2, Capsid protein VP3 (3 entities in total)
• 機能のキーワード: cryo-em, virus, coxsackievirus a16
• 由来する生物種: Coxsackievirus A16; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 87317.75

構造登録者

Jiang, Y.,Huang, Y.,Zhu, R.,Zheng, Q.,Li, S.,Xia, N. (登録日: 2023-11-29, 公開日: 2024-09-04, 最終更新日: 2025-01-15)

主引用文献

Zhu, R.,Wu, Y.,Huang, Y.,Jiang, Y.,Jiang, Y.,Zhang, D.,Sun, H.,Zhou, Z.,Zhou, L.,Weng, S.,Chen, H.,Chen, X.,Ning, W.,Zou, Y.,He, M.,Yang, H.,Deng, W.,Li, Y.,Chen, Z.,Ye, X.,Han, J.,Yin, Z.,Zhao, H.,Liu, C.,Que, Y.,Fang, M.,Yu, H.,Zhang, J.,Luo, W.,Li, S.,Zheng, Q.,Xu, L.,Xia, N.,Cheng, T.
Broadly therapeutic antibody provides cross-serotype protection against enteroviruses via Fc effector functions and by mimicking SCARB2.
Nat Microbiol, 9:2939-2953, 2024

PubMed Abstract: Enteroviruses contain multiple serotypes and can cause severe neurological complications. The intricate life cycle of enteroviruses involving dynamic virus-receptor interaction hampers the development of broad therapeutics and vaccines. Here, using function-based screening, we identify a broadly therapeutic antibody h1A6.2 that potently protects mice in lethal models of infection with both enterovirus A71 and coxsackievirus A16 through multiple mechanisms, including inhibition of the virion-SCARB2 interactions and monocyte/macrophage-dependent Fc effector functions. h1A6.2 mitigates inflammation and improves intramuscular mechanics, which are associated with diminished innate immune signalling and preserved tissue repair. Moreover, cryogenic electron microscopy structures delineate an adaptive binding of h1A6.2 to the flexible and dynamic nature of the VP2 EF loop with a binding angle mimicking the SCARB2 receptor. The coordinated binding mode results in efficient binding of h1A6.2 to all viral particle types and facilitates broad neutralization of enterovirus, therefore informing a promising target for the structure-guided design of pan-enterovirus vaccine.

PubMed: 39424982
DOI: 10.1038/s41564-024-01822-7

実験手法

ELECTRON MICROSCOPY (3.38 Å)