Structural biology of ion transporters

离子转运蛋白的结构生物学

• 批准号: 19002013
• 负责人: TOYOSHIMA Chikashi
• 金额: $ 350.11万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19002013/
• 关键词: イオンポンプ; 膜蛋白質; 結晶解析

In living organisms, concentrations of ions differ substantially across the membranes and form the basis for biological activity such as nerve excitation and muscle contraction. Such differences in ion concentrations are maintained by ion pump proteins, which reside in biological membrane. In this research project, we focused on the calcium and the sodium pumps, and carried out the crystal structure analyses of the reaction intermediates, development of a high yield expression system of mammalian membrane proteins, and that of methods for visualizing biological membranes in the crystals, aiming at the complete understanding of the mechanism and development of drugs for the ion pumps.

在活的生物体中，离子的浓度在膜上有很大的不同，并形成了生物活性的基础，如神经兴奋和肌肉收缩。离子浓度的这种差异由存在于生物膜中的离子泵蛋白维持。本研究以钙离子泵和钠离子泵为研究对象，开展了反应中间体的晶体结构分析、哺乳动物膜蛋白的高效表达系统的开发以及生物膜在晶体中的可视化方法的研究，旨在全面了解离子泵的作用机制和药物开发。

项目成果

Interdomain communication in calcium pump as revealed in the crystal structures with transmembrane inhibitors

• DOI: 10.1073/pnas.0700979104
• 发表时间: 2007-04-03
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Takahashi, Mihoko;Kondou, Youhei;Toyoshima, Chikashi
• 通讯作者: Toyoshima, Chikashi

A structural view on ionpumping by Ca^<2+>-ATPase

Ca^<2>-ATP酶离子泵的结构观点

• 发表时间: 2010
• 作者: M.Suzuki;T.Kato;K.Yamanouchi;C. Toyoshima
• 通讯作者: C. Toyoshima

How processing of aspartylphosphate is coupled to lumenal gating of the ion pathway in the calcium pump

• DOI: 10.1073/pnas.0709978104
• 发表时间: 2007-12-11
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Toyoshima, Chikashi;Norimatsu, Yoshiyuki;Ogawa, Haruo
• 通讯作者: Ogawa, Haruo

Intermediate phosphorylation reactions in the mechanism of ATP utilization by the copper ATPase (CopA) of Thermotoga maritima

• DOI: 10.1074/jbc.m802735200
• 发表时间: 2008-08-15
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Hatori, Yuta;Hirata, Ayami;Inesi, Giuseppe
• 通讯作者: Inesi, Giuseppe

How Ca2+-ATPase pumps ions across the sarcoplasmic reticulum membrane.

• DOI: 10.1016/j.bbamcr.2008.10.008
• 发表时间: 2009-06
• 期刊: Biochimica et biophysica acta
• 作者: C. Toyoshima