7YAR

ZIKV_Fab_G9E

これはPDB形式変換不可エントリーです。

7YAR の概要

• エントリーDOI: 10.2210/pdb7yar/pdb
• EMDBエントリー: 33718
• 分子名称: heavy chain, light chain, E protein, ... (4 entities in total)
• 機能のキーワード: virus complexed with antibody, virus
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 330327.89

構造登録者

Shu, B.,Thiam-Seng, N.,Lok, S. (登録日: 2022-06-28, 公開日: 2023-01-04, 最終更新日: 2025-07-02)

主引用文献

Adams, C.,Carbaugh, D.L.,Shu, B.,Ng, T.S.,Castillo, I.N.,Bhowmik, R.,Segovia-Chumbez, B.,Puhl, A.C.,Graham, S.,Diehl, S.A.,Lazear, H.M.,Lok, S.M.,de Silva, A.M.,Premkumar, L.
Structure and neutralization mechanism of a human antibody targeting a complex Epitope on Zika virus.
Plos Pathog., 19:e1010814-e1010814, 2023

PubMed Abstract: We currently have an incomplete understanding of why only a fraction of human antibodies that bind to flaviviruses block infection of cells. Here we define the footprint of a strongly neutralizing human monoclonal antibody (mAb G9E) with Zika virus (ZIKV) by both X-ray crystallography and cryo-electron microscopy. Flavivirus envelope (E) glycoproteins are present as homodimers on the virion surface, and G9E bound to a quaternary structure epitope spanning both E protomers forming a homodimer. As G9E mainly neutralized ZIKV by blocking a step after viral attachment to cells, we tested if the neutralization mechanism of G9E was dependent on the mAb cross-linking E molecules and blocking low-pH triggered conformational changes required for viral membrane fusion. We introduced targeted mutations to the G9E paratope to create recombinant antibodies that bound to the ZIKV envelope without cross-linking E protomers. The G9E paratope mutants that bound to a restricted epitope on one protomer poorly neutralized ZIKV compared to the wild-type mAb, demonstrating that the neutralization mechanism depended on the ability of G9E to cross-link E proteins. In cell-free low pH triggered viral fusion assay, both wild-type G9E, and epitope restricted paratope mutant G9E bound to ZIKV but only the wild-type G9E blocked fusion. We propose that, beyond antibody binding strength, the ability of human antibodies to cross-link E-proteins is a critical determinant of flavivirus neutralization potency.

PubMed: 36626401
DOI: 10.1371/journal.ppat.1010814

実験手法

ELECTRON MICROSCOPY (5.9 Å)