RGD Reference Report - A virus-induced conformational switch of STAT1-STAT2 dimers boosts antiviral defenses. - Rat Genome Database

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A virus-induced conformational switch of STAT1-STAT2 dimers boosts antiviral defenses.

Authors: Wang, Yuxin  Song, Qiaoling  Huang, Wei  Lin, Yuxi  Wang, Xin  Wang, Chenyao  Willard, Belinda  Zhao, Chenyang  Nan, Jing  Holvey-Bates, Elise  Wang, Zhuoya  Taylor, Derek  Yang, Jinbo  Stark, George R 
Citation: Wang Y, etal., Cell Res. 2021 Feb;31(2):206-218. doi: 10.1038/s41422-020-0386-6. Epub 2020 Aug 5.
RGD ID: 41789624
Pubmed: (View Article at PubMed) PMID:32759968
DOI: Full-text: DOI:10.1038/s41422-020-0386-6

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.



Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Stat2  (signal transducer and activator of transcription 2)

Genes (Mus musculus)
Stat2  (signal transducer and activator of transcription 2)

Genes (Homo sapiens)
STAT2  (signal transducer and activator of transcription 2)


Additional Information