RyR钙释放通道-调节蛋白复合体的结构与功能研究

项目名称： RyR钙释放通道-调节蛋白复合体的结构与功能研究

项目编号： No.31270768

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 尹长城

作者单位： 北京大学

项目金额： 90万元

中文摘要： Ryanodine 受体（RyR）是定位于细胞肌浆网/内质网膜上的离子通道，其功能是在细胞受激时将肌浆网/内质网贮存的Ca2+离子释放至细胞浆内，引发Ca2+激活的生物学过程。RyR在细胞肌浆网原位与多个蛋白相互作用，调节RyR通道的钙释放功能。这些蛋白包括calsequestrin, triadin和junctin。实验表明，这些蛋白与RyR形成一个超分子复合体，调节RyR的结构与功能。虽然分子生物学、生物化学、电生理学实验表明这些调节蛋白与RyR形成超分子复合体并调节RyR/Ca2+释放通道功能，但其结构基础及工作机制尚不清楚。本项目拟以RyR1-调节蛋白复合体为研究对象，应用结构生物学（cryo-EM）结合生物化学、电生理学方法研究调节蛋白与RyR1的相互作用及其对RyR1/Ca2+释放通道功能的影响,阐明调节蛋白与RyR相互作用并调节RyR/Ca2+释放通道的结构基础和工作机制

中文关键词： 蓝尼丁受体；二氢嘧啶受体；冷冻电镜；结构机制；调节机制

英文摘要： Ryanodine receptor(RyR) is an ion channel located in membrane of sarco(endo)plasmic reticulum(SR/ER), which functions as a calcium release channel in response to stimuli to release calcium from SR/ER to initiate calcium-activated biological activities. In situ, RyR interacts with an array of proteins that regulate the calcium release activity of RyR。These prteins include calsequestrin, triadin and junctin.It has been proposed that these proteins form a super molecular complex with RyR to modify its structure and function. Although molecular biology,biochemistry and electrophysiology experiments have sugggested these proteins may form a super molecular complex with RyR and regulate its structure and function, the structural basis and working mechanism are still unknown.In this project, we will use structural biology (cryo-EM) in conmbination with biochemistry and electrophysiology methodologies to investigate the interactions of these regulatory proteins with RyR and their effects on the calcium release channel, to reveal the structural basis and working mechanism of their action.

英文关键词： ryanodine receptor；dihidropyridine receptor；cryo-electron microscopy；structural mechanism；regulatory mechanism