哺乳动物瞬时受体电位离子通道TRPM7的结构与功能研究

中风是威胁我国人民生活健康的重大心脑血管疾病，其高致死致残率对患者和其家人造成重大的负担。但是，目前针对这一重大疾病并无很有效的药物。大鼠的体内实验研究表明，通过抑制或者敲除瞬时受体电位离子通道TRPM7，能够极大地减少脑缺血性锥形神经细胞的死亡，同时还能在较长的时间内保持正常的神经元活性。因此，TRPM7是一种非常有潜力的治疗中风的新型靶点。一旦解析出TRPM7的结构，对治疗中风的药物开发具有非常重要的意义。本研究采用哺乳细胞表达系统大量表达TRPM7蛋白，纯化获得稳定均一的蛋白，之后利用单分子冷冻电镜技术解析TRPM7的三维结构。我们也将对TRPM6和TRPM7复合物进行研究，力争获得复合物结构，为之后中风相关药物的开发提供结构基础。

Stroke is a major cardio-cerebrovascular disease that threatens human life and health in our country. The high morbidity of disability creates a significant burden on patients and their families. However, there are still no effective treatment for stroke. In vivo study of rat brain shows that inhibition or knockdown of Transient Receptor Potential Melastatin 7 ion channel （TRPM7）greatly reduces pyramidal cell death after cerebral ischemia and maintains normal neuronal functions. Therefore, TRPM7 has a great potential to be a new drug target for ischemic stroke. It is of great importance to the development of drugs for the treatment of stroke if we solve the structure of TRPM7. TRPM7 will be overexpressed in mammalian expression system, and then purified with highly stable and homogeneous protein sample. Single particle cryo-electron microscopy will be used to determine the 3-D dimensional structures of TRPM7. Furthermore, our research will be focused on TRPM6 and TRPM7 complex. We will also try to get the structure of TRPM6/7 complex. The structural studies of TRPM7 and TRPM6/7 complex will therefore provide essential insights for the development of improved drug for the treatment of stroke.