Structural physiology of the gastric proton pump
| Project/Area Number |
17H03653
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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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| 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, 准教授 (60596188)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 機能生物化学 / 膜タンパク質 / P型ATPase / 胃プロトンポンプ / 胃 / X線結晶構造解析 / Cryo EM / 能動輸送体 / 構造生物学 / P-type ATPases / 蛋白質 / 構造解析 / P-type ATPase |
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| Outline of Final Research Achievements |
We determined high-resolution structures of the gastric proton pump, which provide molecular basis of how this pump acidify our gastric juice down to pH 1 (Abe et al., 2018, Nature). We also determined K+-bound form of the proton pump to show unequivocally its transport stoichiometry (Yamamoto et al., 2019, eLife).
We further determined crystal and cryoEM structures of phospholipid flippase, and revealed its molecular mechanisms.
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| Academic Significance and Societal Importance of the Research Achievements |
少なくともヒトの組織において最大のイオン濃度勾配を作り出すことのできる胃プロトンポンプの最も重要なメカニズム『どのようにしてpH1もの強酸（胃酸）に対してH+を輸送することができるのかが明らかになった。
不快な胸焼けを伴う胃炎は、胃の中が強い酸性の為に引き起こされる。胃プロトンポンプの高分解能構造は、現在臨床利用される胃酸抑制剤の改良や、新たな作用機序をもった薬剤の論理的設計に資する。
脂質フリッパーゼの構造解析によって、イオンポンプと近縁のタンパク質でありながら、どのようにイオンと比して巨大な基質（リン脂質）を輸送できるのか、その分子メカニズムを明らかにした。
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Report
(5 results)
Research Products
(28 results)
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[Journal Article] Isoform-selective regulation of mammalian cryptochromes2020
Author(s)
Miller Simon、Son You Lee、Aikawa Yoshiki、Makino Eri、Nagai Yoshiko、Srivastava Ashutosh、Oshima Tsuyoshi、Sugiyama Akiko、Hara Aya、Abe Kazuhiro、Hirata Kunio、Oishi Shinya、Hagihara Shinya、Sato Ayato、Tama Florence、Itami Kenichiro、Kay Steve A.、Hatori Megumi、Hirota Tsuyoshi
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Journal Title
Nature Chemical Biology
Volume: -
Issue: 6
Pages: 676-685
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Isoform-selective regulation of mammalian cryptochromes2020
Author(s)
Simon Miller, You Lee Son, Yoshiki Aikawa, Eri Makino, Yoshiko Nagai, Ashutosh Srivastava, Tsuyoshi Oshima, Akiko Sugiyama, Aya Hara, Kazuhiro Abe, Kunio Hirata, Shinya Oishi, Shinya Hagihara, Ayato Sato, Florence Tama, Kenichiro Itami, Steve A. Kay, Megumi Hatori & Tsuyoshi Hirota
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Journal Title
Nat. Chem. Biol.
Volume: in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Purified F-ATP synthase forms a Ca2+dependent high-conductance channel matching the mitochondrial permeability transition pore.2019
Author(s)
Urbani A,Giorgio V,Carrer A, Franchin C,Arrigoni G, Jiko C,Abe K,Maeda S, Sginzawa-Itoh K, Bogers JF, McMillan DG, Gerle C, Szabo I, Bernardi P
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Journal Title
Nature communications
Volume: 4341
Issue: 1
Pages: 4341-4341
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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