The Viral Protein K7 Inhibits Biochemical Activities and Condensate Formation by the DEAD-box Helicase DDX3X.
DDX3X
DEAD-box helicase
RNA helicase
Stress granule
Vaccinia
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
01 10 2023
01 10 2023
Historique:
received:
10
03
2023
revised:
17
06
2023
accepted:
24
07
2023
pmc-release:
01
10
2024
medline:
15
9
2023
pubmed:
31
7
2023
entrez:
30
7
2023
Statut:
ppublish
Résumé
The DEAD-box RNA helicase DDX3X promotes translation initiation and associates with stress granules. A range of diverse viruses produce proteins that target DDX3X, including hepatitis C, dengue, vaccinia, and influenza A. The interaction of some of these viral proteins with DDX3X has been shown to affect antiviral intracellular signaling, but it is unknown whether and how viral proteins impact the biochemical activities of DDX3X and its physical roles in cells. Here we show that the protein K7 from vaccinia virus, which binds to an intrinsically disordered region in the N-terminus of DDX3X, inhibits RNA helicase and RNA-stimulated ATPase activities, as well as liquid-liquid phase separation of DDX3X in vitro. We demonstrate in HCT 116 cells that K7 inhibits association of DDX3X with stress granules, as well as the formation of aberrant granules induced by expression of DDX3X with a point mutation linked to medulloblastoma and DDX3X syndrome. The results show that targeting of the intrinsically disordered N-terminus is an effective viral strategy to modulate the biochemical functions and subcellular localization of DDX3X. Our findings also have potential therapeutic implications for diseases linked to aberrant DDX3X granule formation.
Identifiants
pubmed: 37517790
pii: S0022-2836(23)00316-9
doi: 10.1016/j.jmb.2023.168217
pmc: PMC10528715
mid: NIHMS1921791
pii:
doi:
Substances chimiques
DEAD-box RNA Helicases
EC 3.6.4.13
RNA
63231-63-0
Viral Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
168217Subventions
Organisme : NCI NIH HHS
ID : F30 CA247347
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118088
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR021228
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007250
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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