A bacterial effector deamidates UBC13 to dampen the inflammatory response
| Project/Area Number |
22790403
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SANADA Takahito 東京大学, 医科学研究所, 特任研究員 (00569957)
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| Research Collaborator |
MIZUSHIMA Tsunehiro 兵庫県立大学, 大学院・生命理学研究科, 教授 (90362269)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 病原性大腸菌 / Shigella flexneri / T3SS / 自然免疫 / 脱アミド化 / TRAF6 / NF-kB / UBC13 / 細菌 / 病原性 / 炎症 |
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| Research Abstract |
We show that OspI, a Shigella effector encoded by ORF169b on the large plasmid and delivered via the type III secretion system(T3SS), dampens acute inflammatory responses during bacterial invasion by suppressing the TNF receptor-associated factor 6(TRAF6)-mediated signaling pathway. OspI is a glutamine deamidase that selectively deamidates Gln100 to Glu100 in Ubc13. Consequently, the E2 ubiquitin-conjugating activity required for TRAF6 activation is inhibited, allowing Shigella OspI to modulate the diacylglycerol-CBM(CARD-Bcl10-Malt1) complex-TRAF6-NF-κB signaling pathway. We determined the 2. 0 A crystal structure of OspI, which contains a putative Cys-His-Asp catalytic triad. A mutational analysis showed this catalytic triad to be essential for the deamidation of Ubc13. Our results suggest that Shigella inhibits acute inflammatory responses in the initial stage of infection by targeting the Ubc13-TRAF6 complex.
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Report
(3 results)
Research Products
(6 results)
