8V5Q

Varicella Zoster Virus (VZV) glycoprotein E (gE) gI binding domain in complex with human Fab 1E3

Summary for 8V5Q

• Entry DOI: 10.2210/pdb8v5q/pdb
• Descriptor: Fab 1E3 Heavy Chain, Fab 1E3 Light Chain, Envelope glycoprotein E, ... (6 entities in total)
• Functional Keywords: varicella zoster virus, vzv, ge, glycoprotein e, gi binding domain, fab, 1e3, viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 73666.91

Authors

Holzapfel, G.,Seraj, N.,Harshbarger, W. (deposition date: 2023-11-30, release date: 2024-12-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)