Channel-Transporter Correlation

通道-转运体相关性

基本信息

批准号：
07276103
负责人：
OKADA Yasunobu
金额：
$ 56.19万
依托单位：
Okazaki National Research Institutes
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-07276103/
关键词：
ion channel water channel transporter Ca pump structure-function relation cloning

项目摘要

Structural and functional correlations of channels and/or transporters were investigated from physiological, molecular biological and biochemical points of view. During these three years in this study, new channels (over 29) and new transporters (over 42) were discovered, and their genes were cloned. Structure-function correlations were elucidated by identification of numbers of functional domains and amino acid sites. New types of functional or structural correlation between channels and transporters were also demonstrated (over 10). New diseases were identified to be due to mutations of genes of channels or transporters (over 10). Especially a big progress was achieved in the research of ATP-binding cassette (ABC) transporter proteins. For example, a novel ABC protein cMOAT was cloned and found to mediate the ATP-dependent transport of glutathion-conjugates. The expression of cMOAT was found to be defective in the Dubin-Johnson syndrome. The ATP-sensitive KィイD1+ィエD1 channel was revealed to be a complex of two subunits : SUR1 of the ABC protein family and Kir6.2 of the inward-rectifier KィイD1+ィエD1 channel family. Some of ABC proteins have been found to have more than one activities of transporter, channel and their regulator. For example, P-glycoprotein and CFTR were found to be a regulator for volume-sensitive ClィイD1-ィエD1 channel and ATP release, respectively.

从物理，分子生物学和生化的观点研究了通道和/或转运蛋白的结构和功能相关性。在这三年的这项研究中，发现了新的渠道（超过29个）和新的转运蛋白（超过42），并克隆了它们的基因。通过鉴定功能域和氨基酸位点的数量来阐明结构功能相关性。还展示了通道和转运蛋白之间的新型功能或结构相关性（超过10）。新的疾病被认为是由于通道或转运蛋白基因的突变（超过10）。特别是在ATP结合盒（ABC）转运蛋白的研究中取得了巨大进展。例如，克隆了一种新型的ABC蛋白CMOAT，并发现可以介导谷胱甘肽 - 偶联物的ATP依赖性转运。发现CMOAT的表达在Dubin-Johnson综合征中有缺陷。对ATP敏感的KII D1+IE D1通道揭示为两个亚基的复合物：ABC蛋白家族的SUR1和内向矩阵KII D1+IE D1通道家族的Kir6.2。已经发现，某些ABC蛋白具有多种转运蛋白，通道及其调节剂的活性。例如，发现P-糖蛋白和CFTR分别是体积敏感CLI D1-E D1通道和ATP释放的调节剂。