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@ARTICLE{Zhou:613890,
author = {Zhou, Momei and Vollmer, Benjamin and Machala, Emily and
Chen, Muyuan and Grünewald, Kay and Arvin, Ann M. and Chiu,
Wah and Oliver, Stefan L.},
title = {{T}argeted mutagenesis of the herpesvirus fusogen central
helix captures transition states},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {PUBDB-2024-05669},
pages = {7958},
year = {2023},
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.},
cin = {CSSB-LIV-KG},
ddc = {500},
cid = {I:(DE-H253)CSSB-LIV-KG-20220525},
pnm = {899 - ohne Topic (POF4-899) / DFG project 390874280 - EXC
2155: RESIST - Resolving Infection Susceptibility
(390874280)},
pid = {G:(DE-HGF)POF4-899 / G:(GEPRIS)390874280},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38042814},
UT = {WOS:001115563700027},
doi = {10.1038/s41467-023-43011-w},
url = {https://bib-pubdb1.desy.de/record/613890},
}