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TitleStructural basis for STAT2 suppression by flavivirus NS5.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 10, Page 875-885, Year 2020
Publish dateAug 10, 2020
AuthorsBoxiao Wang / Stephanie Thurmond / Kang Zhou / Maria T Sánchez-Aparicio / Jian Fang / Jiuwei Lu / Linfeng Gao / Wendan Ren / Yanxiang Cui / Ethan C Veit / HeaJin Hong / Matthew J Evans / Seán E O'Leary / Adolfo García-Sastre / Z Hong Zhou / Rong Hai / Jikui Song /
PubMed AbstractSuppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of ...Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral-cellular complex involved. Here, we report the cryo-EM and crystal structures of human STAT2 (hSTAT2) in complex with the non-structural protein 5 (NS5) of Zika virus (ZIKV) and dengue virus (DENV), revealing two-pronged interactions between NS5 and hSTAT2. First, the NS5 methyltransferase and RNA-dependent RNA polymerase (RdRP) domains form a conserved interdomain cleft harboring the coiled-coil domain of hSTAT2, thus preventing association of hSTAT2 with interferon regulatory factor 9. Second, the NS5 RdRP domain also binds the amino-terminal domain of hSTAT2. Disruption of these ZIKV NS5-hSTAT2 interactions compromised NS5-mediated hSTAT2 degradation and interferon suppression, and viral infection under interferon-competent conditions. Taken together, these results clarify the mechanism underlying the functional antagonism of STAT2 by both ZIKV and DENV.
External linksNat Struct Mol Biol / PubMed:32778820 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.01 - 4.0 Å
Structure data

21618

6wcz

EMDB-21618, PDB-6wcz:
CryoEM structure of full-length ZIKV NS5-hSTAT2 complex
Method: EM (single particle) / Resolution: 4.0 Å

PDB-6ux2:
Crystal structure of ZIKV RdRp in complex with STAT2
Method: X-RAY DIFFRACTION / Resolution: 3.01 Å

Chemicals

ChemComp-SO4:
SULFATE ION

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • zika virus
KeywordsDNA BINDING PROTEIN/VIRAL PROTEIN / host-pathogen interaction / VIRAL PROTEIN / DNA BINDING PROTEIN-VIRAL PROTEIN complex / IMMUNE SYSTEM / ZIKV NS5 / hSTAT2 / CryoEM

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