TY  - JOUR
AU  - Zhou, Momei
AU  - Vollmer, Benjamin
AU  - Machala, Emily
AU  - Chen, Muyuan
AU  - Grünewald, Kay
AU  - Arvin, Ann M.
AU  - Chiu, Wah
AU  - Oliver, Stefan L.
TI  - Targeted mutagenesis of the herpesvirus fusogen central helix captures transition states
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - PUBDB-2024-05669
SP  - 7958
PY  - 2023
AB  - 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. 
LB  - PUB:(DE-HGF)16
C6  - pmid:38042814
UR  - <Go to ISI:>//WOS:001115563700027
DO  - DOI:10.1038/s41467-023-43011-w
UR  - https://bib-pubdb1.desy.de/record/613890
ER  -