Structural basis of the inhibition of STAT1 activity by Sendai virus C protein
| Project/Area Number |
25860341
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Virology
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| Research Institution | Hiroshima University |
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Principal Investigator |
ODA Kosuke 広島大学, 大学院医歯薬保健学研究院, 助教 (60571255)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 構造生物 / 自然免疫 / パラミクソウイルス / インターフェロン / FRET / Cタンパク質 / STAT1 / アクセサリータンパク質 / センダイウイルス / X線結晶構造解析 / タンパク質複合体 |
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| Outline of Final Research Achievements |
Sendai virus C protein inhibits the signal transduction pathways of interferon-γ by binding to the N-terminal domain of STAT1 (STAT1ND). We determined the crystal structure of STAT1ND associated with the C-terminal half of the C protein (Y3). The structure showed that two molecules of Y3 symmetrically bind to each niche created between two molecules of the STAT1ND dimer. Molecular modeling suggested that an anti-parallel form of the full-length STAT1 dimer can bind only one Y3 molecule and that a parallel form can bind two Y3 molecules. Our study suggests that C protein interferes with the domain arrangement of STAT1 dimer, leading to the accumulation of phosphorylated STAT1 and the formation of high molecular weight complex in slower kinetic, which is responsible to complete inhibition of transcription. In addition, we discuss the underlying mechanism that the phosphorylation of STAT2 is inhibited in the presence of the C protein after stimulation by IFN-α/β.
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Report
(3 results)
Research Products
(11 results)
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[Presentation] B型肝炎ウイルス蛋白質の性状解析2014
Author(s)
坂口剛正, 川端涼子, 福士雅也, 小田康祐, 入江崇
Organizer
第29回中国四国ウイルス研究会
Place of Presentation
山口大学吉田キャンパス大学会館 (山口県・山口市)
Year and Date
2014-06-28 – 2014-06-29
Related Report
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