| Project/Area Number |
18H02409
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | Institute of Physical and Chemical Research (2022)
Tokyo Institute of Technology (2018-2020) |
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Principal Investigator |
Suzuki Toshiharu 国立研究開発法人理化学研究所, 開拓研究本部, 客員研究員 (60618809)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
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| Keywords | F1-ATPase / X線結晶構造解析 / ATPase / crystal structure / FoF1-ATP syntase / structural biology / motor protein / ATP / X-ray crystallography / motor proteins / 分子モーター / FoF1-ATP合成酵素 |
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| Outline of Final Research Achievements |
In this study, various high-resolution crystal structures of reaction intermediate states of bovine F1-ATPase were determined by using various X-ray crystallographic techniques. The structures obtained enabled us to deeply discuss its continuous structural changes at the atomic level during its ATPase’s turnover. It unveiled valuable molecular mechanisms for driving the rotation induced by phosphate-releasing, determining the release-order of reaction products, ADP and Pi, and for highly-conserved arginine-finger residue. In addition, the substrate binding cleft formed by alpha- and beta-subunits was revealed to shrink by ATP-binding and to stepwisely expand by the following ATP-cleavage and phosphate-release. It provides us to clues to understand the molecular mechanism of molecular motor in light of energy conversion.
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| Academic Significance and Societal Importance of the Research Achievements |
近年多くの蛋白質の立体構造が決定されているが、蛋白質が機能している瞬間を原子レベルで議論できている例は非常に少ない。しかし本研究では高分解能な酵素反応機構中間体構造が多種得られ議論できている。この手法が他酵素に適用できれば、様々な酵素の触媒機能理解に繋がると期待される。また本研究では、筋肉など生体内で多様に利用されているATPaseの分子機構を明らかにした。ATPaseがATPの化学エネルギーから力学的エネルギーを取り出し利用する仕組みの理解は、将来的な人工ナノアクチュエーターの設計や、生命のエネルギーを利用するという、新しいエネルギー獲得・利用法の確立の理論的基盤になると考えられる。
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