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-Structure paper
タイトル | A conformational selection mechanism of flavivirus NS5 for species-specific STAT2 inhibition. |
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ジャーナル・号・ページ | Commun Biol, Vol. 7, Issue 1, Page 76, Year 2024 |
掲載日 | 2024年1月10日 |
著者 | Mahamaya Biswal / Wangyuan Yao / Jiuwei Lu / Jianbin Chen / Juliet Morrison / Rong Hai / Jikui Song / |
PubMed 要旨 | Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ...Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ZIKV NS5s were shown to facilitate proteosome-mediated protein degradation of human STAT2 (hSTAT2). However, how flavivirus NS5s have evolved for species-specific IFN-suppression remains unclear. Here we report structure-function characterization of the DENV serotype 2 (DENV2) NS5-hSTAT2 complex. The MTase and RdRP domains of DENV2 NS5 form an extended conformation to interact with the coiled-coil and N-terminal domains of hSTAT2, thereby promoting hSTAT2 degradation in cells. Disruption of the extended conformation of DENV2/ZIKV NS5, but not the alternative compact state, impaired their hSTAT2 binding. Our comparative structural analysis of flavivirus NS5s further reveals a conserved protein-interaction platform with subtle amino-acid variations likely underpinning diverse IFN-suppression mechanisms. Together, this study uncovers a conformational selection mechanism underlying species-specific hSTAT2 inhibition by flavivirus NS5. |
リンク | Commun Biol / PubMed:38195857 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.34 - 3.45 Å |
構造データ | EMDB-40952, PDB-8t12: EMDB-40953, PDB-8t13: |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | IMMUNE SYSTEM/VIRAL PROTEIN / complex / IMMUNE SYSTEM-VIRAL PROTEIN complex |