细胞外膜Orai1通道是拥有四次跨膜的特殊钙离子通道，具有很高的钙离子选择性，是细胞外钙离子流入细胞的主要离子通道之一。静息态的Orai1通道没有活性，需要另外一个钙离子感受器STIM1结合并进行激活。为了深入了解Orai1通道的结构和功能，我们综合运用电生理、细胞生物学、蛋白质晶体学和冷冻电镜技术，研究以下三个方面内容：激活态Orai1通道突变体筛选，激活态Orai1通道的三维结构测定以及Orai1-STIM1复合物三维结构测定。本项目的研究成果将阐明Orai1选择性地通透钙离子的分子机理，并且揭示STIM1分子结合并激活Orai1通道的分子细节，为自身免疫疾病的防治提供非常重要的分子基础和理论指导意义。

Orai1 channel on plasma membrane is a special calcium channel and contains four transmembrane helices. It has high selectivity over calcium ion. Orai1 channel is one of major channels through which extracellular calcium flux into cytosol. Orai1 channel at resting state has no any activity and requires another calcium sensor STIM1 to bind and then be activated. In order to elucidate the structure and function of Orai1 channel, we comprehensively used the electrophysiology, cell biology , protein crystallography and cryo electron microscopy techniques, to investigate three items: screen of Orai1 mutants at activated state; structure determination of Orai1 channel at activated state and structure determination of STIM1-Orai1 complex. The outcome of this study will uncover the molecular mechanism of high selectivity of calcium ion by Orai1 and the molecular details of Orai1 channel binding by STIM1, providing vital information for autoimmune disease.