Max-Planck-Institute of Biochemistry, Department of Structural Cell Biology, Martinsried, Germany.
Mol Cell. 2012 May 11;46(3):274-86. doi: 10.1016/j.molcel.2012.03.005. Epub 2012 Apr 5.
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 Ska1 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 Å-long molecule. We discuss how this symmetric architecture might complement and stabilize the Ndc80-microtubule attachments with analogies to the yeast Dam1/DASH complex.
Ska 复合物是人类细胞中准确细胞分裂所必需的有丝分裂成分。它由三个亚基组成，共同作用以与 Ndc80 网络协同建立稳定的动粒-微管相互作用。我们表明，Ska 核心复合物的结构是一个由卷曲螺旋相互交织形成的 W 形二聚体，由 Ska1、Ska2 和 Ska3 之间的相互作用形成。Ska1 和 Ska3 的 C 端结构域突出在同源二聚体的每一端，当与中心核心连接时在体外结合微管，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向心性失败，随后细胞死亡。因此，Ska 复合物在 350 Å 长的分子的两端具有二价和协同的微管结合特性。我们讨论了这种对称结构如何通过与酵母 Dam1/DASH 复合物的类比来补充和稳定 Ndc80-微管附着。
