| Project/Area Number |
24870014
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional biochemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
ABE Kazuhiro 名古屋大学, 細胞生理学研究センター, 助教 (60596188)
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 生体エネルギー変換 / 胃プロトンポンプ / P型ATPase / 膜タンパク質 / 極低温電子顕微鏡 / 電子線結晶学 |
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| Research Abstract |
In response to food intake, pH of our stomach reaches around 1. This highly acidic environment is generated by Gastric proton pump, H+,K+-ATPase, therefore a prominent drug target for the acid-related diseases. Besides its significant interest as a drug target, gastric H+,K+-ATPase faces a remarkable task of pumping protons against a million-fold gradient ranging from pH 7 in the cell to 1 in the stomach. Maintaining a potent concentration gradient of six orders of magnitude is hardly met by any other membrane pump in nature. How does the proton pump generate a million-fold H+ gradient?
A key requirement is the transport stoichiometry. By determining a single Rb+-bound structure of H+,K+-ATPase by electron crystallography of 2D crystals prepared by improved carbon sandwich method, we showed the unique structural evidence of 1H+/1Rb+/1ATP transport mode, which is prerequisite for the generation of the potent proton gradient across the membrane.
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