| Project/Area Number |
16K14700
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
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| Research Institution | University of Hyogo |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 蛋白質 / 酵素反応 / ユビキチンリガーゼ / エフェクター |
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| Outline of Final Research Achievements |
Pathogenic bacteria such as Shigella, Salmonella and Yersinia deliver a variety of virulence factors, called effectors, into host cells. Some of effectors hijack host proteins and function as E3 ubiquitin ligases. The NEL domain and CXD motif are different from those of the eukaryotic HECT and RING-finger E3 ligases. To elucidate the molecular mechanisms of bacterial E3 ubiquitin ligase effectors, we performed the structural and functional analyses of YopM and IpaH family proteins. In this study, we solved the crystal structure of Yersinia YopM, which has CXD motif at 2.5A resolution. Shigella effector IpaH9.8 contains leucine-rich repeats (LRRs) involved in substrate recognition and NEL domain. We determined the crystal structures of substrate recognition domain of IpaH9.8. These structures provide insights into the structural features of bacterial E3 ubiquitin ligases.
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| Academic Significance and Societal Importance of the Research Achievements |
腸管病原細菌による炎症性下痢は世界の5歳未満児死亡原因で肺炎に次いで多く、有効なワクチンのない病原菌の存在により発展途上国を中心に多数の死者を出している。また、腸管病原細菌の感染は近年の多剤耐性菌の出現により先進国においても問題となっており病原細菌の感染機構解明や治療法の開発は重要な研究課題である。本研究で決定したエルシニアYopMおよび赤痢IpaH9.8基質認識領域の立体構造は、病原細菌の感染機構の理解に貢献するものである。
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