Microtubule Attachment and Centromeric Tension Shape the Protein Architecture of the Human Kinetochore.
Microtubule Attachment and Centromeric Tension Shape the Protein Architecture of the Human Kinetochore.
复制标题
DOI：
10.1016/j.cub.2020.09.038
复制
发表时间：
2020-12-21
期刊：
影响因子：
--
通讯作者：
Joglekar AP
中科院分区：
文献类型：
--
作者：
Kukreja AA;Kavuri S;Joglekar AP
着丝粒是一种复杂的蛋白质机器，其纳米尺度的蛋白质结构在其染色体分离的分子机制中发挥着不可或缺的作用。然而，在人类细胞中定义这种结构仍然具有挑战性，因为动粒的大小和成分复杂。在这里，我们使用Förster共振能量转移来揭示人类细胞中单个动粒-微管连接的结构。我们发现Ndc80复合体的微管结合域聚集在微管加端。这种聚集只有在微管附着后才发生，并且随着着丝粒张力的增加而成比例增加。令人惊讶的是，Ndc80复合体聚集不依赖于其着丝粒受体的组织和数量。此外，这种聚集在酵母和人类着丝粒中是相似的，尽管它们的着丝粒组织有显著的差异。这些和其他数据表明，人类动粒的微管结合界面就像一块灵活的“草坪”，尽管它是通过重复的生化亚单位成核的。Kukreja等人。使用FRET显微镜来阐明关键的人类动粒蛋白相对于微管加端的纳米级结构。他们的数据突出了微管结合NDC80复合体在人类和萌发中的酵母着丝粒中的保守组织，尽管它们的着丝粒基础明显不同。
The nanoscale protein architecture of the kinetochore, a complex protein machine, plays an integral role in the molecular mechanisms underlying its functions in chromosome segregation. However, defining this architecture in human cells remains challenging because of the large size and compositional complexity of the kinetochore. Here, we use Förster Resonance Energy Transfer to reveal the architecture of individual kinetochore-microtubule attachments in human cells. We find that the microtubule-binding domains of the Ndc80 complex cluster at the microtubule plus-end. This clustering occurs only after microtubule attachment, and it increases proportionally with centromeric tension. Surprisingly, Ndc80 complex clustering is independent of the organization and number of its centromeric receptors. Moreover, this clustering is similar in yeast and human kinetochores despite significant differences in their centromeric organizations. These and other data suggest that the microtubule-binding interface of the human kinetochore behaves like a flexible “lawn” despite being nucleated by repeating biochemical subunits. Kukreja et al. use FRET microscopy to elucidate the nanoscale architecture of key human kinetochore proteins relative to the microtubule plus-end. Their data highlight a conserved organization of the microtubule-binding Ndc80 complex in the human and budding yeast kinetochores despite their significantly different centromeric foundations.
登录
查看更多内容
影响因子：
21.3
作者：
Aravamudhan P;Goldfarb AA;Joglekar AP
通讯作者：
Joglekar AP
影响因子：
64.5
作者：
Ciferri, Claudio;Pasqualato, Sebastiano;Musacchio, Andrea
通讯作者：
Musacchio, Andrea
DOI：
10.1073/pnas.1718553115
发表时间：
2018-03-13
影响因子：
11.1
作者：
Helgeson LA;Zelter A;Riffle M;MacCoss MJ;Asbury CL;Davis TN
通讯作者：
Davis TN
伪GTPASE CENP-M驱动人类动物组件。
影响因子：
7.7
作者：
Basilico F;Maffini S;Weir JR;Prumbaum D;Rojas AM;Zimniak T;De Antoni A;Jeganathan S;Voss B;van Gerwen S;Krenn V;Massimiliano L;Valencia A;Vetter IR;Herzog F;Raunser S;Pasqualato S;Musacchio A
通讯作者：
Musacchio A
DOI：
10.1083/jcb.201403081
发表时间：
2014-08-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hornung P;Troc P;Malvezzi F;Maier M;Demianova Z;Zimniak T;Litos G;Lampert F;Schleiffer A;Brunner M;Mechtler K;Herzog F;Marlovits TC;Westermann S
通讯作者：
Westermann S