| Project/Area Number |
16H06294
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Nureki Osamu 東京大学, 大学院理学系研究科(理学部), 教授 (10272460)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 耕一 東京大学, 大学院新領域創成科学研究科, 教授 (10262073)
MATURANA ANDRES 名古屋大学, 生命農学研究科, 准教授 (10452004)
加藤 英明 東京大学, 大学院総合文化研究科, 准教授 (80805961)
石谷 隆一郎 東京大学, 大学院理学系研究科(理学部), 特任教授 (90361568)
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| Project Period (FY) |
2016-04-26 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥563,290,000 (Direct Cost: ¥433,300,000、Indirect Cost: ¥129,990,000)
Fiscal Year 2020: ¥87,100,000 (Direct Cost: ¥67,000,000、Indirect Cost: ¥20,100,000)
Fiscal Year 2019: ¥99,710,000 (Direct Cost: ¥76,700,000、Indirect Cost: ¥23,010,000)
Fiscal Year 2018: ¥124,800,000 (Direct Cost: ¥96,000,000、Indirect Cost: ¥28,800,000)
Fiscal Year 2017: ¥111,670,000 (Direct Cost: ¥85,900,000、Indirect Cost: ¥25,770,000)
Fiscal Year 2016: ¥140,010,000 (Direct Cost: ¥107,700,000、Indirect Cost: ¥32,310,000)
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| Keywords | 生物物理 / 電子顕微鏡 / X線 / 蛋白質 / Ｘ線 |
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| Outline of Final Research Achievements |
We elucidated molecular mechanisms of membrane proteins regulated by physical stimuli (light, sound, heat, membrane potential, osmotic pressure). For light perception, we elucidated dynamics of ChR by time-resolved X-ray crystallography. Moreover, we determined the crystal structures of rhodopsin proteins such as Chrimson, HeR, SzR and Rh-PDE, and elucidated molecular mechanisms of their functions. We also determined the structures of Prestin, a voltage-dependent membrane motor protein involved sound amplification, TRPV3 channel sensing heat, voltage-gated potassium channel Kv4 complexed with two regulatory subunits, CALHM ATP channel, voltage-gated Cl- channel VCCN, osmotic pressure-sensing LRRC8 by a single molecular analysis of Cryo-EM, and elucidated their molecular mechanisms.
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| Academic Significance and Societal Importance of the Research Achievements |
研究開始当初ほぼ未解決であった物理的刺激が膜蛋白質を活性化するメカニズムを解明したことにより、膜蛋白質における輸送制御機構の解明に大きく貢献した。また膜蛋白質は生理学的に重要な機能を持ち、膜蛋白質の変異は重篤な疾病を惹起する。実際、創薬のターゲットの約半数は、膜受容体や膜輸送体であることから、本研究成果は解明した構造に基づいた疾患の治療薬の設計や開発に寄与することが期待される。
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| Assessment Rating |
Verification Result (Rating)
A
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Assessment Rating |
Result (Rating)
A: Progress in the research is steadily towards the initial goal. Expected research results are expected.
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