The Disordered Spindly C-terminus Interacts with RZZ Subunits ROD-1 and ZWL-1 in the Kinetochore through the Same Sites in C. Elegans.
The Disordered Spindly C-terminus Interacts with RZZ Subunits ROD-1 and ZWL-1 in the Kinetochore through the Same Sites in C. Elegans.
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DOI：
10.1016/j.jmb.2021.166812
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发表时间：
2021-02-19
影响因子：
5.6
通讯作者：
Vögeli B
中科院分区：
文献类型：
--
作者：
Henen MA;Myers W;Schmitt LR;Wade KJ;Born A;Nichols PJ;Vögeli B
纺锤体是细胞分裂过程中参与染色体分离的动力蛋白接头。Spindly的n端结构域与微管马达动力蛋白及其激活剂动力蛋白结合，而c端结构域（Spindly- c）与着丝点最外层的ROD/ZW10/ZWILCH （RZZ）复合物结合。在人类中，spindy - c与ROD结合，而在秀丽隐杆线虫中，spindy - c与Zwilch （ZWL-1）和ROD-1结合。本文采用多种生物物理技术对秀丽隐杆线虫Spindly-C的结构、动力学和相互作用位点进行了表征。我们发现，尽管整体失调，但有两个区域具有可变的α-螺旋倾向。其中一个区域位于c端一半，结构紧凑；第二种是稀疏分布在n端一半。与ROD-1和ZWL-1的相互作用主要是由Spindly-C的两个相同的顺序远程紊乱片段介导的，这两个片段在c端与螺旋区相邻。研究结果表明，在线虫中，在ROD-1/ZWL-1复合物环境中，ROD-1上的spindl - c结合位点被ZWL-1屏蔽或构象减弱，因此只有ZWL-1直接与spindl - c相互作用。
Spindly is a dynein adaptor involved in chromosomal segregation during cell division. While Spindly’s N-terminal domain binds to the microtubule motor dynein and its activator dynactin, the C-terminal domain (Spindly-C) binds its cargo, the ROD/ZW10/ZWILCH (RZZ) complex in the outermost layer of the kinetochore. In humans, Spindly-C binds to ROD, while in C. elegans Spindly-C binds to both Zwilch (ZWL-1) and ROD-1. Here, we employed various biophysical techniques to characterize the structure, dynamics and interaction sites of C. elegans Spindly-C. We found that despite the overall disorder, there are two regions with variable α-helical propensity. One of these regions is located in the C-terminal half and is compact; the second is sparsely populated in the N-terminal half. The interactions with both ROD-1 and ZWL-1 are mostly mediated by the same two sequentially remote disordered segments of Spindly-C, which are C-terminally adjacent to the helical regions. The findings suggest that the Spindly-C binding sites on ROD-1 in the ROD-1/ZWL-1 complex context are either shielded or conformationally weakened by the presence of ZWL-1 such that only ZWL-1 directly interacts with Spindly-C in C. elegans.
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影响因子：
3.3
作者：
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Higgins, D. G.
DOI：
10.1146/annurev-cellbio-100814-125438
发表时间：
2015
影响因子：
11.3
作者：
Cianfrocco MA;DeSantis ME;Leschziner AE;Reck-Peterson SL
通讯作者：
Reck-Peterson SL