IMP/IMBA Bioinformatics Core Facility, Research Institute of Molecular Pathology, Dr. Bohr Gasse 7, 1030 Vienna, Austria.
Nat Cell Biol. 2012 May 6;14(6):604-13. doi: 10.1038/ncb2493.
Centromeres direct the assembly of kinetochores, microtubule-attachment sites that allow chromosome segregation on the mitotic spindle. Fundamental differences in size and organization between evolutionarily distant eukaryotic centromeres have in many cases obscured general principles of their function. Here we demonstrate that centromere-binding proteins are highly conserved between budding yeast and humans. We identify the histone-fold protein Cnn1(CENP-T) as a direct centromere receptor of the microtubule-binding Ndc80 complex. The amino terminus of Cnn1 contains a conserved peptide motif that mediates stoichiometric binding to the Spc24-25 domain of the Ndc80 complex. Consistent with the critical role of this interaction, artificial tethering of the Ndc80 complex through Cnn1 allows mini-chromosomes to segregate in the absence of a natural centromere. Our results reveal the molecular function of CENP-T proteins and demonstrate how the Ndc80 complex is anchored to centromeres in a manner that couples chromosome movement to spindle dynamics.
着丝粒指导着动粒的组装，而动粒是微管附着的位点，可使染色体在有丝分裂纺锤体上进行分离。在进化上相距甚远的真核生物着丝粒之间在大小和组织上存在着根本的差异，这在很多情况下掩盖了它们功能的一般原则。在这里，我们证明了芽殖酵母和人类之间的着丝粒结合蛋白高度保守。我们确定组蛋白折叠蛋白 Cnn1（CENP-T）是微管结合 Ndc80 复合物的直接着丝粒受体。Cnn1 的氨基末端含有一个保守的肽基序，可与 Ndc80 复合物的 Spc24-25 结构域进行化学计量结合。该相互作用的关键作用一致，通过 Cnn1 人为地束缚 Ndc80 复合物可以允许微型染色体在没有天然着丝粒的情况下进行分离。我们的结果揭示了 CENP-T 蛋白的分子功能，并证明了 Ndc80 复合物如何以一种将染色体运动与纺锤体动力学偶联的方式锚定到着丝粒上。
