Journal Article

PUBDB-2024-05669

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Targeted mutagenesis of the herpesvirus fusogen central helix captures transition states

Zhou, M. (Corresponding author) ; Vollmer, B. ; Machala, E. ; Chen, M. ; Grünewald, K. ; Arvin, A. M. ; Chiu, W. ; Oliver, S. L.

2023
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-023-43011-w  doi:10.3204/PUBDB-2024-05669

Abstract: Herpesviruses remain a burden for animal and human health, including the medically important varicella-zoster virus (VZV). Membrane fusion mediated by conserved core glycoproteins, the fusogen gB and the heterodimer gH-gL, enables herpesvirus cell entry. The ectodomain of gB orthologs has five domains and is proposed to transition from a prefusion to postfusion conformation but the functional relevance of the domains for this transition remains poorly defined. Here we describe structure-function studies of the VZV gB DIII central helix targeting residues $^{526}$EHV$^{528}$. Critically, a H527P mutation captures gB in a prefusion conformation as determined by cryo-EM, a loss of membrane fusion in a virus free assay, and failure of recombinant VZV to spread in cell monolayers. Importantly, two predominant cryo-EM structures of gB[H527P] are identified by 3D classification and focused refinement, suggesting they represented gB conformations in transition. These studies reveal gB DIII as a critical element for herpesvirus gB fusion function.

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Contributing Institute(s):

1. CSSB - Leibniz-Institut für Experimentelle Virologie (LIV) - Kay Grünewald (CSSB-LIV-KG)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)
2. DFG project 390874280 - EXC 2155: RESIST - Resolving Infection Susceptibility (390874280) (390874280)

Experiment(s):

1. No specific instrument

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