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@ARTICLE{Royet:292524,
author = {A. Royet and R. Ruedas and L. Gargowitsch and V. Gervais
and J. Habersetzer and L. Pieri and M. Ouldali and M.
Paternostre and I. Hofmann$^*$ and T. Tubiana and S.
Fieulaine and S. Bressanelli},
title = {{N}onstructural protein 4 of human norovirus self-assembles
into various membrane-bridging multimers.},
journal = {The journal of biological chemistry},
volume = {300},
issn = {0021-9258},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {DKFZ-2024-01770},
pages = {107724},
year = {2024},
note = {Volume 300, Issue 9, September 2024, 107724 / Core Facility
Antibodies},
abstract = {Single-stranded, positive-sense RNA ((+)RNA) viruses
replicate their genomes in virus-induced intracellular
membrane compartments. (+)RNA viruses dedicate a significant
part of their small genomes (a few thousands to a few tens
of thousands of bases) to the generation of these
compartments by encoding membrane-interacting proteins
and/or protein domains. Noroviruses are a very diverse genus
of (+)RNA viruses including human and animal pathogens.
Human noroviruses are the major cause of acute
gastroenteritis worldwide, with genogroup II genotype 4
(GII.4) noroviruses accounting for the vast majority of
infections. Three viral proteins encoded in the N-terminus
of the viral replication polyprotein direct intracellular
membrane rearrangements associated with norovirus
replication. Of these three, nonstructural protein 4 (NS4)
seems to be the most important, although its exact functions
in replication organelle formation are unknown. Here we
produce, purify and characterize GII.4 NS4. AlphaFold
modeling combined with experimental data refine and correct
our previous crude structural model of NS4. Using simple
artificial liposomes, we report an extensive
characterization of the membrane properties of NS4. We find
that NS4 self-assembles and thereby bridges liposomes
together. Cryo-EM, NMR and membrane flotation show formation
of several distinct NS4 assemblies, at least two of them
bridging pairs of membranes together in different fashions.
Noroviruses belong to (+)RNA viruses whose replication
compartment is extruded from the target endomembrane and
generates double-membrane vesicles. Our data establish that
the 21-kDa GII.4 human norovirus NS4 can, in the absence of
any other factor, recapitulate in tubo several features,
including membrane apposition, that occur in such
processes.},
keywords = {Cryo-electron microscopy (Other) / Lipid-protein
interaction (Other) / Liposome (Other) / Membrane (Other) /
Nonstructural protein (Other) / Norovirus (Other) /
Plus-stranded RNA virus (Other) / Protein assembly (Other) /
Viral protein (Other) / Viral replication (Other)},
cin = {A190},
ddc = {540},
cid = {I:(DE-He78)A190-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39214299},
doi = {10.1016/j.jbc.2024.107724},
url = {https://inrepo02.dkfz.de/record/292524},
}