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-Structure paper
| タイトル | Structural basis for STAT2 suppression by flavivirus NS5. |
|---|---|
| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 27, Issue 10, Page 875-885, Year 2020 |
| 掲載日 | 2020年8月10日 |
著者 | Boxiao 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 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:32778820 / PubMed Central |
| 手法 | EM (単粒子) / X線回折 |
| 解像度 | 3.01 - 4.0 Å |
| 構造データ | EMDB-21618, PDB-6wcz: ![]() PDB-6ux2: |
| 化合物 | ![]() ChemComp-SO4: ![]() ChemComp-ZN: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | DNA 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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homo sapiens (ヒト)
zika virus (ジカ熱ウイルス)
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