A virus-induced conformational switch of STAT1-STAT2 dimers boosts antiviral defenses.
Animals
Chlorocebus aethiops
Fibroblasts
/ metabolism
HEK293 Cells
HeLa Cells
Herpes Simplex
/ metabolism
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phosphorylation
/ genetics
Protein Conformation
Protein Multimerization
/ genetics
RNA Interference
Rhabdoviridae Infections
/ metabolism
STAT1 Transcription Factor
/ chemistry
STAT2 Transcription Factor
/ chemistry
Signal Transduction
/ genetics
Simplexvirus
/ metabolism
Vero Cells
Vesicular stomatitis Indiana virus
/ metabolism
Journal
Cell research
ISSN: 1748-7838
Titre abrégé: Cell Res
Pays: England
ID NLM: 9425763
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
26
03
2020
accepted:
16
07
2020
pubmed:
8
8
2020
medline:
21
12
2021
entrez:
8
8
2020
Statut:
ppublish
Résumé
Type I interferons (IFN-I) protect us from viral infections. Signal transducer and activator of transcription 2 (STAT2) is a key component of interferon-stimulated gene factor 3 (ISGF3), which drives gene expression in response to IFN-I. Using electron microscopy, we found that, in naive cells, U-STAT2, lacking the activating tyrosine phosphorylation, forms a heterodimer with U-STAT1 in an inactive, anti-parallel conformation. A novel phosphorylation of STAT2 on T404 promotes IFN-I signaling by disrupting the U-STAT1-U-STAT2 dimer, facilitating the tyrosine phosphorylation of STATs 1 and 2 and enhancing the DNA-binding ability of ISGF3. IKK-ε, activated by virus infection, phosphorylates T404 directly. Mice with a T-A mutation at the corresponding residue (T403) are highly susceptible to virus infections. We conclude that T404 phosphorylation drives a critical conformational switch that, by boosting the response to IFN-I in infected cells, enables a swift and efficient antiviral defense.
Identifiants
pubmed: 32759968
doi: 10.1038/s41422-020-0386-6
pii: 10.1038/s41422-020-0386-6
pmc: PMC7405385
doi:
Substances chimiques
STAT1 Transcription Factor
0
STAT1 protein, human
0
STAT2 Transcription Factor
0
STAT2 protein, human
0
Stat1 protein, mouse
0
Stat2 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
206-218Subventions
Organisme : NCI NIH HHS
ID : P01 CA062220
Pays : United States
Organisme : NIH HHS
ID : S10 OD023436
Pays : United States
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