Structural basis for molecular mechanisms of substrate recognition and transport regulation by membrane transporters

膜转运蛋白底物识别和转运调节的分子机制的结构基础

• 批准号: 20227003
• 负责人: NUREKI Osamu
• 金额: $ 133.04万
• 依托单位: The University of Tokyo (2009-2012)Tokyo Institute of Technology (2008)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008-05-12 至 2013-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20227003/
• 关键词: X 線結晶構造解析; チャネル; トランスポーター; 電気生理学解析; 遺伝学解析; X線結晶構造解析; 計算機シミュレーション; パッチクランプ; 膜輸送体; 電気生理学; 遺伝学

Membrane transporters maintain the intracellular circumstances by strictly regulating the import and export of metal ions, sugars, metabolites and drugs etc. To elucidate (A) how the transporters drive their transport, (B) how the transporters exclusively select their specific substrates and (C) how the transporters regulate their transporting activities at at an atomic resolution, we performed (1) structure determination by X-ray crystallography, (2) dynamic property analysis by MD simulation and (3) in vivo and in vitro complementary experiments, focusing on ion transporters of magnesium, iron and heavy metals, light-gated cation channels, protein transporters, peptide transporter and multidrug transporters. Especially, we uncovered the essential molecular mechanism of membrane transport by comparing and integrating the functional mechanisms of transporters specific for various kinds of target solutes.

膜转运蛋白通过严格调节金属离子、糖、代谢物和药物等的输入和输出来维持细胞内环境。为了阐明（A）转运蛋白如何驱动其转运，（B）转运蛋白如何排他性地选择其特异性底物以及（C）转运蛋白如何在原子分辨率下调节其转运活性，我们进行了（1）X射线晶体学结构测定，（2）分子动力学模拟动力学特性分析;（3）体内外互补实验，重点研究镁、铁、重金属离子转运蛋白、光门控阳离子通道、蛋白质转运蛋白、多肽转运蛋白和多药转运蛋白。特别是通过比较和整合各种靶溶质特异性转运蛋白的功能机制，揭示了膜转运的基本分子机制。

项目成果

VIII European Symposium of The Protein Society

第八届蛋白质学会欧洲研讨会

• 发表时间: 2009
• 作者: T.Tsukazaki;H.Mori;K.Ito;O.Nureki;O.Nureki;O. Nureki
• 通讯作者: O. Nureki

ピロリジン翻訳直行性のメカニズム

吡咯烷平移正交性机制

• 发表时间: 2010
• 作者: 塚崎智也;濡木理;野澤佳世,石谷隆一郎
• 通讯作者: 野澤佳世,石谷隆一郎

細胞工学

细胞工程

• 发表时间: 2007
• 作者: 井本逸勢;稲澤譲治
• 通讯作者: 稲澤譲治

Structure of complexes of multidrug exporter and screened cyclic peptides for structure-based inhibitor design

多药输出蛋白和筛选环肽复合物的结构，用于基于结构的抑制剂设计

• 发表时间: 2012
• 作者: R.Ishitani(4名);O.Nureki;O. Nureki
• 通讯作者: O. Nureki

Structural Basis for Dynamic Protein Translocation Across Plasma membrane by Sec Machinery

Sec Machinery 跨质膜动态蛋白质易位的结构基础

• 发表时间: 2011
• 作者: R.Ishitani(4名);O.Nureki;O. Nureki;O. Nureki;O.Nureki;Osamu Nureki
• 通讯作者: Osamu Nureki