细胞周期的有序进行是细胞发挥正常功能的基础。APC/C是细胞周期调控过程中重要的E3泛素连接酶复合体，负责催化细胞周期蛋白的多聚泛素化。单独的APC/C没有活性，需要结合激活子蛋白Cdh1而识别底物。研究发现人体Rev7蛋白通过结合Cdh1而抑制了APC/C的活性。为了激活APC/C并促进细胞周期的进行，细胞因子Ran可以竞争性结合Rev7而引起Cdh1的释放。有趣的是，痢疾杆菌效应因子IpaB也特异性靶向Rev7而异常激活APC/C。目前这些过程中Rev7相关复合物的分子细节还不清楚。在最近的工作中，我们解析了Rev7-Ran的晶体结构，摸索到了Rev7-IpaB的晶体，也获得了稳定均一的Rev7-Cdh1样品，以此为基础，本项目拟研究与比较Rev7-Cdh1，Rev7-Ran及Rev7-IpaB三个复合物的晶体结构，进一步揭示Rev7在细胞周期调控过程中影响APC/C活性的作用机制。

The regulation of cell cycle is the basis of the normal function of cells. APC/C is an important E3 ubiquitin ligase complex in cell cycle regulation, which is responsible for the poly-ubiquitination of Cyclin. APC/C alone does not have the activity until binds to the activator protein Cdh1 to identify substrates. Previous studies indicated that the human Rev7 protein inhibits the activity of APC/C by binding to Cdh1. In order to activate APC/C and promote cell cycle, Ran can compete with Rev7 and cause Cdh1 release. Interestingly, the Shigella effector protein IpaB also specifically targeted Rev7 leading to abnormal activation of APC/C. The molecular details of Rev7-related complexes are still not clear at present. In recent studies, we solved the crystal structure of Rev7-Ran complex, obtained crystals of Rev7-IpaB complex, and acquired a uniform and stable Rev7-Cdh1 protein sample. Based on these results, this project intends to study and compare crystal structures of Rev-Cdh1, Rev7-Ran and Rev7-IpaB complex, and reveal Rev7’s functions in cell cycle regulation by controlling APC/C activity.