6LB0

The cryo-EM structure of HEV VLP in complex with Fab 8C11

6LB0 の概要

• エントリーDOI: 10.2210/pdb6lb0/pdb
• EMDBエントリー: 0866
• 分子名称: Protein ORF2 (1 entity in total)
• 機能のキーワード: hev, neutralizing antibody, immune-complex, virus like particle
• 由来する生物種: Hepatitis E virus (HEV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51303.06

構造登録者

Zheng, Q.,He, M.,Li, S. (登録日: 2019-11-13, 公開日: 2019-12-04, 最終更新日: 2024-03-27)

主引用文献

Zheng, Q.,Jiang, J.,He, M.,Zheng, Z.,Yu, H.,Li, T.,Xue, W.,Tang, Z.,Ying, D.,Li, Z.,Song, S.,Liu, X.,Wang, K.,Zhang, Z.,Wang, D.,Wang, Y.,Yan, X.,Zhao, Q.,Zhang, J.,Gu, Y.,Li, S.,Xia, N.
Viral neutralization by antibody-imposed physical disruption.
Proc.Natl.Acad.Sci.USA, 2019

PubMed Abstract: In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.

PubMed: 31818956
DOI: 10.1073/pnas.1916028116

実験手法

ELECTRON MICROSCOPY (3.6 Å)