Analysis of structure and function of viral proteins that suppress innate immunity
| Project/Area Number |
24590554
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ODA Kosuke 広島大学, 大学院医歯薬保健学研究院, 助教 (60571255)
IRIE Takashi 広島大学, 大学院医歯薬保健学研究院, 准教授 (70419498)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ウイルス / アクセサリー蛋白質 / 自然免疫 / インターフェロン / 蛋白質結晶化 / 蛋白質構造解析 / 共結晶化 / STAT1 |
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| Outline of Final Research Achievements |
We investigated the mechanism by which an accessory protein of Sendai virus, the C protein, inhibits the STAT1 function. We determined the crystal structure of STAT1ND associated with the C-terminal half of the C protein (Y3). Molecular modeling suggested that a parallel form of the STAT1 dimer can bind two Y3 molecules. Kinetic analysis demonstrated anti-cooperative binding of two Y3 molecules with the STAT1 dimer, thereby implying that the second Y3 molecule can only target the STAT1 dimer in a parallel form. STAT1 with excess amounts of Y3 was prone to be phosphorylated at Tyr705 as shown by an in vitro dephosphorylation assay. Since it is reported that the full-length C protein induces a high molecular weight complex of pY-STAT1, the results of this study suggest that the C protein induces complex formation of the parallel form of pY-STAT1, leading to inhibition of transcription.
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Report
(4 results)
Research Products
(10 results)
