Molecular architecture of a cylindrical self-assembly at human centrosomes
Molecular architecture of a cylindrical self-assembly at human centrosomes
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DOI：
10.1038/s41467-019-08838-2
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发表时间：
2019-03-11
影响因子：
16.6
通讯作者：
Lee, Kyung S.
中科院分区：
文献类型：
--
作者：
Kim, Tae-Sung;Zhang, Liang;Lee, Kyung S.
细胞是由不同结构成分之间复杂的相互作用而形成的高级结构和细胞器。中心体是一个无膜的细胞器，由两个微管衍生的结构（称为中心粒）和一个无定形的中心粒周围物质组成。超分辨率显微镜分析显示，在各种生物体的不同pericentriolar材料蛋白质集中定位在一个中心粒周围的高度组织化的方式。然而，这些组织的分子本质仍然未知。在这里，我们表明，两个人的pericentriolar材料支架，Cep 63和Cep 152，合作产生一个异四聚体的α-螺旋束，其功能与其相邻的疏水基序，自组装成一个更高阶的圆柱形结构，能够招募下游组件，包括Plk 4，一个关键的调节中心粒复制。破坏自组装的突变废除Plk 4介导的中心粒复制。由于中心体周围的物质组织在进化上是保守的，这项工作可能为研究各种生物体中中心体支架的组装和功能提供一个范例。
The cell is constructed by higher-order structures and organelles through complex interactions among distinct structural constituents. The centrosome is a membraneless organelle composed of two microtubule-derived structures called centrioles and an amorphous mass of pericentriolar material. Super-resolution microscopic analyses in various organisms revealed that diverse pericentriolar material proteins are concentrically localized around a centriole in a highly organized manner. However, the molecular nature underlying these organizations remains unknown. Here we show that two human pericentriolar material scaffolds, Cep63 and Cep152, cooperatively generate a heterotetrameric alpha-helical bundle that functions in conjunction with its neighboring hydrophobic motifs to self-assemble into a higher-order cylindrical architecture capable of recruiting downstream components, including Plk4, a key regulator for centriole duplication. Mutations disrupting the self-assembly abrogate Plk4-mediated centriole duplication. Because pericentriolar material organization is evolutionarily conserved, this work may offer a paradigm for investigating the assembly and function of centrosomal scaffolds in various organisms.