7SFW

CryoEM structure of Venezuelan Equine Encephalitis virus (VEEV) TC-83 strain VLP in complex with Fab hVEEV-63 (focus refine of the asymmetric unit)

7SFW の概要

• エントリーDOI: 10.2210/pdb7sfw/pdb
• EMDBエントリー: 25102 25103 25104
• 分子名称: Spike glycoprotein E1, Spike glycoprotein E2, Capsid protein, ... (6 entities in total)
• 機能のキーワード: vlp, veev, viral protein, fab, virus-immune system complex, virus/immune system
• 由来する生物種: Venezuelan equine encephalitis virus (strain TC-83) (VEEV); 詳細
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 606579.25

構造登録者

Binshtein, E.,Crowe, J.E. (登録日: 2021-10-04, 公開日: 2022-03-16, 最終更新日: 2024-10-30)

主引用文献

Kafai, N.M.,Williamson, L.E.,Binshtein, E.,Sukupolvi-Petty, S.,Gardner, C.L.,Liu, J.,Mackin, S.,Kim, A.S.,Kose, N.,Carnahan, R.H.,Jung, A.,Droit, L.,Reed, D.S.,Handley, S.A.,Klimstra, W.B.,Crowe, J.E.,Diamond, M.S.
Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge.
J.Exp.Med., 219:-, 2022

PubMed Abstract: Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. A 3.2-Å cryo-electron microscopy reconstruction of VEEV virus-like particles bound by a human Fab suggests that antibody engagement of the B domain may result in cross-linking of neighboring spikes to prevent conformational requirements for viral fusion. Prophylaxis or postexposure therapy with these mAbs protected mice against lethal aerosol challenge with VEEV. Our study defines functional and structural mechanisms of mAb protection and suggests that multiple antigenic determinants on VEEV can be targeted for vaccine or antibody-based therapeutic development.

PubMed: 35297953
DOI: 10.1084/jem.20212532

実験手法

ELECTRON MICROSCOPY (3.2 Å)