美国怀特黑德生物医学研究所Iain M. Cheeseman和美国宾夕法尼亚大学Ekaterina L. Grishchuk研究团队合作揭示，高阶蛋白质组装控制着丝点的形成。这一研究成果发表在2024年1月2日出版的国际学术期刊《自然—细胞所生物学》上。

为了研究高阶组装对着丝粒形成的影响，他们在人类细胞中使用两种不同的基因工程系统生成了内着丝粒蛋白CENP-T的低聚物。尽管单个的CENP-T分子与外部着丝点蛋白的相互作用很差，但模拟着丝点CENP-T密度的低聚物会明显触发功能的细胞质着丝点样颗粒的形成。无论是在细胞内还是在体外，每个寡聚化的CENP-T分子都比单体的CENP-T分子募集更高水平的外着丝点组分。

他们的研究表明，CENP-T的密度依赖性限制了外部着丝粒向着丝粒的募集，在着丝粒中，密集的CENP-A募集了高浓度的内部着丝粒蛋白。

研究人员表示，为了在脊椎动物有丝分裂过程中准确地分离染色体，着丝点-微管相互作用必须限制在每条染色体上的单个位点。先前关于成对的着丝粒蛋白相互作用的研究，无法确定在低密度的CENP-A核小体区域阻止外着丝粒形成的机制。

附：英文原文

Title: Higher-order protein assembly controls kinetochore formation

Author: Sissoko, Gunter B., Tarasovetc, Ekaterina V., Marescal, Ocane, Grishchuk, Ekaterina L., Cheeseman, Iain M.

Issue&Volume: 2024-01-02

Abstract: To faithfully segregate chromosomes during vertebrate mitosis, kinetochore–microtubule interactions must be restricted to a single site on each chromosome. Prior work on pair-wise kinetochore protein interactions has been unable to identify the mechanisms that prevent outer kinetochore formation in regions with a low density of CENP-A nucleosomes. To investigate the impact of higher-order assembly on kinetochore formation, we generated oligomers of the inner kinetochore protein CENP-T using two distinct, genetically engineered systems in human cells. Although individual CENP-T molecules interact poorly with outer kinetochore proteins, oligomers that mimic centromeric CENP-T density trigger the robust formation of functional, cytoplasmic kinetochore-like particles. Both in cells and in vitro, each molecule of oligomerized CENP-T recruits substantially higher levels of outer kinetochore components than monomeric CENP-T molecules. Our work suggests that the density dependence of CENP-T restricts outer kinetochore recruitment to centromeres, where densely packed CENP-A recruits a high local concentration of inner kinetochore proteins.

DOI: 10.1038/s41556-023-01313-7

Source: https://www.nature.com/articles/s41556-023-01313-7