| Project/Area Number |
17K15091
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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 |
Functional biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
Hizukuri Yohei 京都大学, ウイルス・再生医科学研究所, 助教 (70568930)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 膜タンパク質 / 膜内切断プロテアーゼ / Rhomboid / べん毛 / III型分泌装置 / 翻訳後修飾 / アシル化 / 品質管理 / kinetics解析 / 大腸菌 / 基質認識 / 質量分析 / ロンボイド / Ⅲ型分泌装置 / タンパク質分解 |
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| Outline of Final Research Achievements |
Regulated intramembrane proteolysis are found in all kingdoms of life from bacteria to human and known to be involved in various important cellular events. FliO, one of the components of the flagellar type III secretion apparatus, has been found to receive proteolytic cleavage by the rhomboid intramembrane protease homologue GlpG in Escherichia coli. Purpose of this study is to clarify the detailed mechanism and its physiological role of the intramembrane proteolysis of FliO by GlpG. This study revealed that GlpG may have a role for quality control of FliO in the membrane through its cleavage. Surprisingly, this study uncovered that FliO receives not only intramembrane proteolysis by GlpG but also novel N-terminal modifications in the extramembrane space. Such post-transcriptional modification has never been reported. These findings will become the basis for the research on a novel mechanism for post-transcriptional regulation of function of FliO and other membrane proteins.
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| Academic Significance and Societal Importance of the Research Achievements |
膜内切断プロテアーゼはアルツハイマー病やパーキンソン病などの重大な遺伝病の発症メカニズムや微生物病原性などに深く関わるが、その普遍的メカニズムや細胞機能における役割の理解は未だ十分ではない。その分子的・酵素学的理解は創薬開発にもつながる重要な課題である。本研究では大腸菌RhomboidプロテアーゼGlpGの新奇基質FliOの切断の詳細な分子機構とともにその機能調節に関わる生理的役割を明らかにした。FliOはO157など病原性細菌の毒性発揮にも関与するIII型分泌装置の形成に必須の因子であり、その機能発現・維持機構の一端を明らかにすることは細菌感染医療分野においても大きな意義がある。
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