| Project/Area Number |
16H02499
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biophysics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
椛島 佳樹 東京大学, 定量生命科学研究所, 助教 (00580573)
小川 治夫 東京大学, 定量生命科学研究所, 准教授 (40292726)
金井 隆太 東京大学, 定量生命科学研究所, 助教 (50598472)
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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 |
¥43,030,000 (Direct Cost: ¥33,100,000、Indirect Cost: ¥9,930,000)
Fiscal Year 2018: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2017: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2016: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
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| Keywords | イオンポンプ / 膜蛋白質 / 結晶解析 / エネルギー変換 / 構造生物学 / 蛋白質 / 生物物理 |
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| Outline of Final Research Achievements |
We have been aiming at complete understanding of the mechanism of active ion transport and eventually “why the structures of ion pumps have to be so” in particular with the Ca2+-pump for which we have determined atomic structures of 10 reaction intermediates. In this project, we succeeded in elucidating the crystal structures of the gating residue mutants and thereby why proton countertransport is necessary. We also succeeded in determining the crystal structure of the Ca2+ pump with bound ATP in the absence of Ca2+, thereby elucidating structural changes that ATP binding alone can cause. Furthermore, we succeeded in visualising lipid bilayers in the crystals of Ca2+-pump in four states and described detailed interactions with phospholipids and their roles in structural changes.
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| Academic Significance and Societal Importance of the Research Achievements |
イオンポンプは生体の恒常性の維持に極めて重要な役割を持つ膜蛋白質であり、心臓病や癌、神経疾患の治療などの観点からも注目されている。Ca2+ポンプに関しては11の中間状態の構造決定に成功しているのみならず、本研究によって構造変化におけるプロトンの役割や脂質二重膜との相互作用の詳細の解明にまで成功した唯一の膜蛋白質である。原子構造に基づく蛋白質の作動機構の理解がここまで進んだ蛋白質は他に無く、学術的価値は極めて高い。
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