%0 Journal Article
%A Zhou, Momei
%A Vollmer, Benjamin
%A Machala, Emily
%A Chen, Muyuan
%A Grünewald, Kay
%A Arvin, Ann M.
%A Chiu, Wah
%A Oliver, Stefan L.
%T Targeted mutagenesis of the herpesvirus fusogen central helix captures transition states
%J Nature Communications
%V 14
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M PUBDB-2024-05669
%P 7958
%D 2023
%X 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 <sup>526</sup>EHV<sup>528</sup>. 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. 
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38042814
%U <Go to ISI:>//WOS:001115563700027
%R 10.1038/s41467-023-43011-w
%U https://bib-pubdb1.desy.de/record/613890