钙释放激活的钙（CRAC）通道是细胞调节钙信号的重要方式，参与免疫细胞的活化、癌症的发生、细胞的分化和凋亡等多种重要生理功能。近年来，CRAC通道的激活机制成为该领域的研究热点，尤其是钙感受器蛋白STIM1如何和通道蛋白ORAI1相互作用并调控通道的开放状态。本项目将基于课题组前期CRAC通道的研究结果，利用双色超高分辨显微成像技术、X射线晶体学等方法，研究STIM1/ORAI1复合物在细胞中的精确定位以及三维晶体结构，以期找到STIM1/ORAI相互作用方式的关键位点，阐明CARC通道的功能调控方式。本项目的实施有助于揭示CRAC通道开放的分子调控机制，为综合性免疫缺陷症、癌症等相关疾病提供潜在的治疗靶点。

Calcium release-activated calcium channel is a vital regulator of cellular calcium signaling, engaging in several important processes such as cell proliferation and apoptosis, tumorigenesis and activation of immunocytes. Recently, the activation mechanism of CRAC channel has becoming a reseach hotspot, especially how calcium sensor protein STIM1 interacts with channel protein ORAI1 and mediates the pore's opening. Based on our previous work, we will focus on the in situ localization profile and 3D crystal structure of STIM1/ORAI1 complex by using super-resolution imaging, X-ray crystallography，hoping to find the interaction pattern of STIM1/ORAI1 complex and how it related to CRAC channel's activity. This project aims to explore the activation mechanism of CRAC channel, which may help to provide a new therapeutic target in autoimmunity diseases and cancer.