Oligomer structure and functional regulation in cation pumps

阳离子泵中的低聚物结构和功能调节

• 批准号: 10044048
• 负责人: TANIGUCHI Kazuya
• 金额: $ 7.74万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10044048/
• 关键词: Na; K-ATPase; oligomer; P-Type ATPase; Post Albers Scheme; tetraprotomer; H; リン酸化; フォスファターゼ; 構造変化; Naポンプ; Hポンプ

Since the discovery of Na/K-ATPase, evidence has accumulated to suggest that 1 mol of ATP hydrolysis occurs via the Na^+-occluded ADP-sensitive phosphoenzyme, the K^+- sensitive phoshphoenzyme and the K^+-occluded enzyme accompanying active transport of 3Na^+ and 2K^+ according the Post-Albers sheme. However, some controversial issues have arisen concerning whether the functional unit of the enzyme is an αβ-protomer or a much higher oligomer, which would be related to the mechanism of transport, either sequential or simultaneous. Detailed studies of oligomer interaction and the reactivity of the enzyme and a comparison of the extent of phosphorylation with ligand-binding capacities in the presence or absence of ATP hydrolysis and others strongly suggest that the functional unit of the enzyme in the membrane is a tetraprotomer, (αβ)_4. They also suggest that each reaction intermediate of the Post-Albers scheme, respectively, reflects half of the site property of the intermediate and that another half binds ATP.These data may be useful not only to answer the long-standing question of whether the mechanism functions in the presence of both Na^+ and K^+ but also contribute to a better understanding of the mechanism of P-type pump ATPase in general.

自从Na/K-ATP酶被发现以来，越来越多的证据表明，1 mol ATP的水解是通过Na^+封闭的ADP敏感性磷酸酶、K^+敏感性磷酸酶和K^+封闭的酶进行的，根据Post-Albers模型，这些酶伴随着3 Na ^+和2K^+的主动转运。然而，关于该酶的功能单元是αβ-原聚体还是更高级的寡聚体，这与顺序或同时转运机制有关，出现了一些有争议的问题。对寡聚体相互作用和酶的反应性的详细研究以及在存在或不存在ATP水解的情况下磷酸化程度与配体结合能力的比较等都强烈地表明，膜中酶的功能单元是四元体（αβ）_4。他们还认为，Post-Albers方案中的每个反应中间体分别反映了中间体的一半位点性质，另一半则与ATP结合。这些数据不仅有助于回答长期存在的问题，即该机制是否在Na^+和K^+同时存在的情况下发挥作用，而且有助于更好地理解P型泵ATP酶的一般机制。

项目成果

T.Yokoyama, et. al.: "ATP induced fluorescence changes of a bipm and an rh-421 probes in pig kidney Na/K-ATPase"The Na/K-ATPase and Related ATPases (K.Taniguchi and S.Kaya eds.). 237-240 (2000)

T.横山，等。

K.Taniguchi, et.al.: "New aspects of Na/K-ATPase : Acid labile ATP and/or ADP/Pi binding to the tetraprotomer, (αβ)_4"Control and Diseases of Sodium Dependent Transport Proteins and Ion Channels (Y.Suketa, E.Carafoli et. al. eds.). 15-18 (2000)

K.Taniguchi 等人：“Na/K-ATP 酶的新方面：酸不稳定 ATP 和/或 ADP/Pi 与四原体结合，(αβ)_4”钠依赖性转运蛋白和离子通道的控制和疾病（ Y.Suketa，E.Carafoli 等人。15-18 (2000)。

T.Imagawa: "Does Binding of Ouabain to Human α1 Subunit of Na,K-ATPase Affect the ATPase Activity of Adjacent Rat α1 Subunit?" Jpn.J.Pharmacal.vol.76. 415-423 (1998)

T.Imakawa：“哇巴因与人 Na,K-ATP 酶 α1 亚基的结合会影响相邻大鼠 α1 亚基的 ATP 酶活性吗？”Jpn.J.Pharmacal.vol.76 (1998)。

T.Yokoyama, et.al.: "ATP induced fluorescence changes of a bipm and an rh-421 probes in pig kidney Na-K-ATPase"The Na/K-ATPase and Related ATPases (K.Taniguchi and S.Kaya eds.). 455-458 (2000)

T.Yokoyama 等人：“猪肾 Na-K-ATP 酶中 bipm 和 rh-421 探针的 ATP 诱导荧光​​变化”Na/K-ATP 酶和相关 ATP 酶（K.Taniguchi 和 S.Kaya 编辑）

M.Kanagawa, et.al.: "N-terminal phosphorylation of gastric H/K-ATPase both in vitro an in vivo"The Na/K-ATPase and Related ATPases(K.Taniguchi and S.Kaya eds.). 587-590 (2000)

M.Kanakawa 等人：“胃 H/K-ATP 酶在体外和体内的 N 末端磷酸化”Na/K-ATP 酶和相关 ATP 酶（K.Taniguchi 和 S.Kaya 编辑）。