Ki-67 acts as a biological surfactant to disperse mitotic chromosomes.
Ki-67 acts as a biological surfactant to disperse mitotic chromosomes.
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DOI：
10.1038/nature18610
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发表时间：
2016-07-14
期刊：
影响因子：
64.8
通讯作者：
Gerlich DW
中科院分区：
文献类型：
--
作者：
Cuylen S;Blaukopf C;Politi AZ;Müller-Reichert T;Neumann B;Poser I;Ellenberg J;Hyman AA;Gerlich DW
真核生物基因组分裂成染色体，染色体在有丝分裂过程中形成紧密且空间分离良好的机械体。这使得染色体能够彼此独立地移动，以便将基因组的一个拷贝精确地分离到每个新生的子细胞中。尽管对有丝分裂染色体的空间组织有了深入的了解，并且在染色体表面发现了蛋白质，但有丝分裂染色体个性的分子和生物物理基础仍然不清楚。我们报告说，Ki-67是有丝分裂染色体外周的一个组成部分，可以防止染色体在核膜解体后坍塌成单个染色质团，从而使染色体独立运动并与有丝分裂纺锤体有效相互作用。Ki-67的染色体分离功能并不局限于特定的蛋白结构域，而是与明显缺乏二级结构的截断突变体的大小和净电荷有关。这表明Ki-67形成了一个空间和电屏障，类似于表面活性剂（表面活性剂）在溶剂中分散颗粒或相分离的液滴。荧光相关光谱显示Ki-67的高表面密度，双色标记显示两个蛋白质末端的分子构象延伸，表明刷状排列是聚合物表面活性剂的特征。因此，我们的研究阐明了有丝分裂染色体外围的生物力学作用，并表明天然蛋白质可以在细胞内区隔化中发挥表面活性剂的作用。
Eukaryotic genomes are partitioned into chromosomes, which during mitosis form compact and spatially well-separated mechanical bodies.This enables chromosomes to move independently of each other for segregation of precisely one copy of the genome to each of the nascent daughter cells. Despite insights into the spatial organization of mitotic chromosomes and the discovery of proteins at the chromosome surface, the molecular and biophysical basis of mitotic chromosome individuality have remained unclear. We report that Ki-67, a component of the mitotic chromosome periphery, prevents chromosomes from collapsing into a single chromatin mass after nuclear envelope disassembly, thus enabling independent chromosome motility and efficient interactions with the mitotic spindle. The chromosome separation function of Ki-67 is not confined within a specific protein domain but correlates with size and net charge of truncation mutants that apparently lack secondary structure. This suggests that Ki-67 forms a steric and electrical barrier, similar to surface-active agents (surfactants) that disperse particles or phase-separated liquid droplets in solvents. Fluorescence correlation spectroscopy showed a high surface density of Ki-67 and dual-color labeling of both protein termini revealed an extended molecular conformation, indicating brush-like arrangements that are characteristic for polymeric surfactants. Our study thus elucidates a biomechanical role of the mitotic chromosome periphery and suggests that natural proteins can function as surfactants in intracellular compartmentalization.