Sun Lingfei, Guan Ruifang, Lee I-Ju, Liu Yajun, Chen Mengran, Wang Jiawei, Wu Jian-Qiu, Chen Zhucheng
MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Science, Tsinghua University, Beijing 100084, China.
Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
Dev Cell. 2015 May 26;33(4):413-26. doi: 10.1016/j.devcel.2015.03.003. Epub 2015 May 7.
Anillins and Mid1 are scaffold proteins that play key roles in anchorage of the contractile ring at the cell equator during cytokinesis in animals and fungi, respectively. Here, we report crystal structures and functional analysis of human anillin and S. pombe Mid1. The combined data show anillin contains a cryptic C2 domain and a Rho-binding domain. Together with the tethering PH domain, three membrane-associating elements synergistically bind to RhoA and phospholipids to anchor anillin at the cleavage furrow. Surprisingly, Mid1 also binds to the membrane through a cryptic C2 domain. Dimerization of Mid1 leads to high affinity and preference for PI(4,5)P2, which stably anchors Mid1 at the division plane, bypassing the requirement for Rho GTPase. These findings uncover the unexpected general machinery and the divergent regulatory logics for the anchorage of the contractile ring through the anillin/Mid1 family proteins from yeast to humans.
Anillins和Mid1是支架蛋白，分别在动物和真菌细胞分裂期间将收缩环锚定在细胞赤道上发挥关键作用。在此，我们报告了人类Anillin和粟酒裂殖酵母Mid1的晶体结构及功能分析。综合数据表明，Anillin包含一个隐蔽的C2结构域和一个Rho结合结构域。与系留PH结构域一起，三个膜结合元件协同结合RhoA和磷脂，将Anillin锚定在分裂沟处。令人惊讶的是，Mid1也通过一个隐蔽的C2结构域与膜结合。Mid1的二聚化导致对PI(4,5)P2具有高亲和力和偏好性，从而将Mid1稳定地锚定在分裂平面上，绕过了对Rho GTP酶的需求。这些发现揭示了通过从酵母到人类的Anillin/Mid1家族蛋白锚定收缩环的意外通用机制和不同的调控逻辑。
