Structural and Functional Organization of the Ska Complex, a Key Component of the Kinetochore-Microtubule Interface
Structural and Functional Organization of the Ska Complex, a Key Component of the Kinetochore-Microtubule Interface
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DOI：
10.1016/j.molcel.2012.03.005
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发表时间：
2012-05-11
期刊：
影响因子：
16
通讯作者：
Conti, Elena
中科院分区：
文献类型：
--
作者：
Jeyaprakash, A. Arockia;Santamaria, Anna;Conti, Elena
Ska复合物是人类细胞中精确细胞分裂所需的基本有丝分裂组分。它由三个亚基组成，它们共同发挥作用，与Ndc 80网络一起建立稳定的激动剂-微管相互作用。我们发现，Ska核心复合物的结构是一个W形的卷曲螺旋的二聚体，由Ska 1，Ska 2和Ska 3之间的相互作用交织而成。Ska 1和Ska 3的C-末端结构域在同二聚体的每一端突出，当连接到中央核心时在体外结合微管，并且在体内是必需的。破坏中央卷曲螺旋或二聚化界面的突变导致染色体聚集失败，随后细胞死亡。因此，斯卡复合物在350埃长的分子的末端具有二分和合作的微管蛋白结合特性。我们讨论了这种对称的架构可能会补充和稳定的Ndc 80微管附件与类比酵母Dam 1/DASH复合物。
The Ska complex is an essential mitotic component required for accurate cell division in human cells. It is composed of three subunits that function together to establish stable kinetochore-microtubule interactions in concert with the Ndc80 network. We show that the structure of the Ska core complex is a W-shaped dimer of coiled coils, formed by intertwined interactions between Ska1, Ska2, and Ska3. The C-terminal domains of Skal and Ska3 protrude at each end of the homodimer, bind microtubules in vitro when connected to the central core, and are essential in vivo. Mutations disrupting the central coiled coil or the dimerization interface result in chromosome congression failure followed by cell death. The Ska complex is thus endowed with bipartite and cooperative tubulin-binding properties at the ends of a 350 angstrom-long molecule. We discuss how this symmetric architecture might complement and stabilize the Ndc80-microtubule attachments with analogies to the yeast Dam1/DASH complex.