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Structure and regulation of the microtubule plus-end tracking protein Kar9
Structure ( IF 4.4 ) Pub Date : 2021-07-07 , DOI: 10.1016/j.str.2021.06.012
Anil Kumar 1 , Sandro M Meier 2 , Ana-Maria Farcas 3 , Cristina Manatschal 1 , Yves Barral 3 , Michel O Steinmetz 4
Affiliation  

In many eukaryotes, coordination of chromosome segregation with cell cleavage relies on the patterned interaction of specific microtubules with actin filaments through dedicated microtubule plus-end tracking proteins (+TIPs). However, how these +TIPs are spatially controlled is unclear. The yeast +TIP Kar9 drives one of the spindle aster microtubules along actin cables to align the mitotic spindle with the axis of cell division. Here, we report the crystal structure of Kar9's folded domain, revealing spectrin repeats reminiscent of the +TIPs MACF/ACF7/Shot and PRC1/Ase1. Point mutations abrogating spectrin-repeat-mediated dimerization of Kar9 reduced and randomized Kar9 distribution to microtubule tips, and impaired spindle positioning. Six Cdk1 sites surround the Kar9 dimerization interface. Their phosphomimetic substitution inhibited Kar9 dimerization, displaced Kar9 from microtubules, and affected its interaction with the myosin motor Myo2. Our results provide molecular-level understanding on how diverse cell types may regulate and pattern microtubule-actin interactions to orchestrate their divisions.



中文翻译:

微管加端跟踪蛋白Kar9的结构与调控

在许多真核生物中,染色体分离与细胞分裂的协调依赖于特定微管与肌动蛋白丝通过专用微管加端跟踪蛋白 (+TIP) 的模式化相互作用。然而,这些 +TIP 如何在空间上受到控制尚不清楚。酵母+TIP Kar9 沿着肌动蛋白电缆驱动一个纺锤体微管,使有丝分裂纺锤体与细胞分裂轴对齐。在这里,我们报告了 Kar9 折叠结构域的晶体结构,揭示了类似于 +TIP MACF/ACF7/Shot 和 PRC1/Ase1 的血影蛋白重复。消除血影蛋白重复介导的 Kar9 二聚化的点突变减少和随机化 Kar9 分布到微管尖端,并损害纺锤体定位。六个 Cdk1 位点围绕着 Kar9 二聚化界面。它们的磷模拟取代抑制了 Kar9 二聚化,将 Kar9 从微管中置换出来,并影响了它与肌球蛋白运动 Myo2 的相互作用。我们的研究结果提供了关于不同细胞类型如何调节和模式微管-肌动蛋白相互作用以协调它们的分裂的分子水平的理解。

更新日期:2021-07-07
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