8V5L

Structure of the Varicella Zoster Virus (VZV) gI binding domain of glycoprotein E (gE) in complex with human Fab 1A2 and 1E12

8V5L の概要

• エントリーDOI: 10.2210/pdb8v5l/pdb
• 分子名称: Fab 1A2 Heavy Chain, Fab 1A2 Light Chain, Envelope glycoprotein E, ... (5 entities in total)
• 機能のキーワード: glycoprotein, ge, vzv, varicella zoster, viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 123590.37

構造登録者

Seraj, N.,Holzapfel, G.,Harshbarger, W. (登録日: 2023-11-30, 公開日: 2024-10-09, 最終更新日: 2024-11-13)

主引用文献

Harshbarger, W.D.,Holzapfel, G.,Seraj, N.,Tian, S.,Chesterman, C.,Fu, Z.,Pan, Y.,Harelson, C.,Peng, D.,Huang, Y.,Chandramouli, S.,Malito, E.,Bottomley, M.J.,Williams, J.
Structures of the Varicella Zoster Virus Glycoprotein E and Epitope Mapping of Vaccine-Elicited Antibodies.
Vaccines (Basel), 12:-, 2024

PubMed Abstract: Varicella zoster virus (VZV) is the causative agent for chickenpox and herpes zoster (HZ, shingles). HZ is a debilitating disease affecting elderly and immunocompromised populations. Glycoprotein E (gE) is indispensable for viral replication and cell-to-cell spread and is the primary target for anti-VZV antibodies. Importantly, gE is the sole antigen in Shingrix, a highly efficacious, AS01-adjuvanted vaccine approved in multiple countries for the prevention of HZ, yet the three-dimensional (3D) structure of gE remains elusive. : We sought to determine the structure of VZV gE and to understand in detail its interactions with neutralizing antibodies. : We used X-ray crystallography and cryo-electron microscopy to elucidate structures of gE bound by recombinant Fabs of antibodies previously elicited through vaccination with Zostavax, a live, attenuated vaccine. : The 3D structures resolve distinct central and C-terminal antigenic domains, presenting an array of diverse conformational epitopes. The central domain has two beta-sheets and two alpha helices, including an IgG-like fold. The C-terminal domain exhibits 3 beta-sheets and an Ig-like fold and high structural similarity to HSV1 gE. : gE from VZV-infected cells elicits a human antibody response with a preference for the gI binding domain of gE. These results yield insights to VZV gE structure and immunogenicity, provide a framework for future studies, and may guide the design of additional herpesvirus vaccine antigens. Structures of varicella zoster virus glycoprotein E reveal distinct antigenic domains and define epitopes for vaccine-elicited human antibodies.

PubMed: 39460278
DOI: 10.3390/vaccines12101111

実験手法

X-RAY DIFFRACTION (3.09 Å)