研究人员描述了组装到微管上的芽殖酵母外动粒Ndc80和Dam1环复合物的冷冻电镜结构。复合物的组装是通过多个界面进行的,Dam1内的一个钉书针有助于环的组装。干扰关键界面会抑制酵母的活力。力破裂试验表明,这是动粒-微管连接受损的结果。Ndc80-Dam1环复合体界面和Dam1钉书针上存在纠错磷酸化位点,这解释了动粒-微管附着是如何失稳和重置的。
据介绍,在细胞分裂过程中,动粒将染色体偶联到有丝分裂纺锤体上以分离基因组。误差校正机制驱动动粒-微管附着物的周转,直到实现双向定向。动粒介导的染色体分离如何完成和调节的结构基础仍然是一个悬而未决的问题。
附:英文原文
Title:
Author: Kyle W. Muir, Christopher Batters, Tom Dendooven, Jing Yang, Ziguo Zhang, Alister Burt, David Barford
Issue&Volume: 2023-12-08
Abstract: Kinetochores couple chromosomes to the mitotic spindle to segregate the genome during cell division. An error correction mechanism drives the turnover of kinetochore-microtubule attachments until biorientation is achieved. The structural basis for how kinetochore-mediated chromosome segregation is accomplished and regulated remains an outstanding question. In this work, we describe the cryo–electron microscopy structure of the budding yeast outer kinetochore Ndc80 and Dam1 ring complexes assembled onto microtubules. Complex assembly occurs through multiple interfaces, and a staple within Dam1 aids ring assembly. Perturbation of key interfaces suppresses yeast viability. Force-rupture assays indicated that this is a consequence of impaired kinetochore-microtubule attachment. The presence of error correction phosphorylation sites at Ndc80-Dam1 ring complex interfaces and the Dam1 staple explains how kinetochore-microtubule attachments are destabilized and reset.
DOI: adj8736
Source: https://www.science.org/doi/10.1126/science.adj8736