Molecular Architecture of the Yeast Monopolin Complex
Molecular Architecture of the Yeast Monopolin Complex
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DOI：
10.1016/j.celrep.2012.05.012
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发表时间：
2012-06-01
期刊：
影响因子：
8.8
通讯作者：
Harrison, Stephen C.
中科院分区：
文献类型：
--
作者：
Corbett, Kevin D.;Harrison, Stephen C.
酿酒酵母单核蛋白复合体通过介导减数分裂I纺锤体上的姐妹动粒的共定向来指导减数分裂I中的染色体分离。单核蛋白亚基Csm 1和Lrs 4形成一个V形复合体，可以直接交联姐妹着丝粒。我们在这里报告的monopolin复合物亚基Mam 1和Hrr 25和完整的四蛋白monopolin复合物的生化特性。通过纯化具有不同亚基组合的monopolin亚复合物，我们确定了完整monopolin复合物的化学计量和整体结构。我们已经确定了晶体结构的CSM 1结合到Mam 1片段，显示Mam 1如何包裹周围的CSM 1二聚体，并改变了CSM 1的kinetochore蛋白结合的化学计量。我们进一步表明，Hrr 25的激酶活性被Mam 1结合改变，我们确定Mam 1上的Hrr 25磷酸化位点可能会影响单核蛋白复合物的稳定性和/或减数分裂中的动粒结合。
The Saccharomyces cerevisiae monopolin complex directs proper chromosome segregation in meiosis I by mediating co-orientation of sister kinetochores on the meiosis I spindle. The monopolin subunits Csm1 and Lrs4 form a V-shaped complex that may directly crosslink sister kinetochores. We report here biochemical characterization of the monopolin complex subunits Mam1 and Hrr25 and of the complete four-protein monopolin complex. By purifying monopolin subcomplexes with different subunit combinations, we have determined the stoichiometry and overall architecture of the full monopolin complex. We have determined the crystal structure of Csm1 bound to a Mam1 fragment, showing how Mam1 wraps around the Csm1 dimer and alters the stoichiometry of kinetochore-protein binding by Csm1. We further show that the kinase activity of Hrr25 is altered by Mam1 binding, and we identify Hrr25 phosphorylation sites on Mam1 that may affect monopolin complex stability and/or kinetochore binding in meiosis.