6AJ7

The structure of Enterovirus D68 mature virion in complex with Fab 15C5

6AJ7 の概要

• エントリーDOI: 10.2210/pdb6aj7/pdb
• EMDBエントリー: 9633
• 分子名称: VL of Fab 15C5, VH of Fab 15C5, Capsid protein VP1, ... (5 entities in total)
• 機能のキーワード: enterovirus d68, neutralizing antibody, immune-complex, virus
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 112067.33

構造登録者

Zheng, Q.B.,Zhu, R.,Xu, L.F.,He, M.Z.,Yan, X.D.,Cheng, T.,Li, S.W. (登録日: 2018-08-27, 公開日: 2018-11-07, 最終更新日: 2024-10-16)

主引用文献

Zheng, Q.,Zhu, R.,Xu, L.,He, M.,Yan, X.,Liu, D.,Yin, Z.,Wu, Y.,Li, Y.,Yang, L.,Hou, W.,Li, S.,Li, Z.,Chen, Z.,Li, Z.,Yu, H.,Gu, Y.,Zhang, J.,Baker, T.S.,Zhou, Z.H.,Graham, B.S.,Cheng, T.,Li, S.,Xia, N.
Atomic structures of enterovirus D68 in complex with two monoclonal antibodies define distinct mechanisms of viral neutralization
Nat Microbiol, 4:124-133, 2019

PubMed Abstract: Enterovirus D68 (EV-D68) undergoes structural transformation between mature, cell-entry intermediate (A-particle) and empty forms throughout its life cycle. Structural information for the various forms and antibody-bound capsids will facilitate the development of effective vaccines and therapeutics against EV-D68 infection, which causes childhood respiratory and paralytic diseases worldwide. Here, we report the structures of three EV-D68 capsid states representing the virus at major phases. We further describe two original monoclonal antibodies (15C5 and 11G1) with distinct structurally defined mechanisms for virus neutralization. 15C5 and 11G1 engage the capsid loci at icosahedral three-fold and five-fold axes, respectively. To block viral attachment, 15C5 binds three forms of capsids, and triggers mature virions to transform into A-particles, mimicking engagement by the functional receptor ICAM-5, whereas 11G1 exclusively recognizes the A-particle. Our data provide a structural and molecular explanation for the transition of picornavirus capsid conformations and demonstrate distinct mechanisms for antibody-mediated neutralization.

PubMed: 30397341
DOI: 10.1038/s41564-018-0275-7

実験手法

ELECTRON MICROSCOPY (3.6 Å)