大电导钙激活钾离子通道(BK)的结构与功能研究

项目名称： 大电导钙激活钾离子通道(BK)的结构与功能研究

项目编号： No.31270790

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： 吴允昆

作者单位： 中国科学院福建物质结构研究所

项目金额： 80万元

中文摘要： 大电导钙激活电压依赖性钾离子通道（BK）调控最基本的许多生理过程，其基因突变或结构功能异常与众多疾病密切相关。BK因其出众的高电导及其电压和配体双重调控特性，而备受关注。我们解析的BK门控环晶体结构为研究BK胞内多因子调控提供了全新的模型平台。但是，BK的门控调节机制十分复杂，还需要更明确的阐述。因此，该项目将以X-射线晶体学为主的结构生物学结合生物化学、生物物理和电生理等方法，继续BK 门控环、BK辅助亚基及其与不同调控分子的复合体的结构与功能研究。深入开展BK通道的结构与功能研究将系统地阐释BK的调控机制，并有助于理解其功能特性和致病机理，为BK门控调节性药物的研发奠定基础。

中文关键词： 离子通道；蛋白表达；晶体结构；BK；调控

英文摘要： Large-conductance Ca(2+)-activated K(+) Channels (BK) play essential roles for the regulation of many fundamental physiological processes including smooth muscle tone and neuronal excitability. Their structural and functional abnormalities are associated with many diseases. BK channels are characterized by their large conductance and activation property by both membrane potential and intracellular Ca2+ concentration, so that BKs have attracted much attention in this research field. The solved crystal structure of BK gating ring presentd a model basis for the study of modulation mechanisms of BKs by intracellular multiple factors. However, the mechanisms for BK gating are very complex and further investigations are needed for a better elucidation. Therefore, in-depth structural and functional studies of BK complexes will contribute to a comprehensive understanding of gating mechanisms of BK channels, thus providing the possibilies for effective targeting BKs to treat related diseases.

英文关键词： ion channel；protein expression；crystal structure；BK；modulation