2022 Fiscal Year Final Research Report
Structural and functional analysis of mechanosensitive channel TMC proteins
| Project/Area Number |
20K15754
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | チャネル / 膜タンパク質 / クライオ電子顕微鏡 / 単粒子解析 |
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| Outline of Final Research Achievements |
Mechanosensitive channel TMC1/TMC2 proteins interact with auxiliary subunits to form the mechanoelectrical transduction (MET) channel complex in hair cells. In this study, we aimed to elucidate the molecular mechanisms of ion permeation and mechanosensitive gating of TMC1/2 using cryo-EM single particle analysis. Expanding from the original plan, we successfully prepared complexes of TMC and CIB proteins, which are the component of the MET channel complex, and performed the structural analysis of the TMC-CIB complex.
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| Free Research Field |
構造生命科学
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| Academic Significance and Societal Importance of the Research Achievements |
TMCタンパク質を含む複合体解析の基盤が整ったことで、イオン透過機構のみならず、補助サブユニットによるMETチャネル複合体の活性調節機構の理解にも繋がる点で学術的意義がある。今後、補助サブユニットも含めたMETチャネル複合体の構造機能研究へと展開していく。また、METチャネル複合体は聴覚に関わることから、本研究の成果と今後の展開は難聴の病態理解を深め、構造情報に基づいた薬剤開発の可能性を提供すると期待される。
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