Molecular architecture of a cylindrical self-assembly at human centrosomes

Tae-Sung Kim, Liang Zhang, Jong Ahn, Lingjun Meng, Yang Chen, Eunhye Lee, Jeong Kyu Bang, Jung Mi Lim, Rodolfo Ghirlando, Lixin Fan, Yun-Xing Wang, Bo Yeon Kim, Jung-Eun Park and Kyung S. Lee ()
Additional contact information
Tae-Sung Kim: National Institutes of Health
Liang Zhang: National Institutes of Health
Jong Ahn: National Institutes of Health
Lingjun Meng: National Institutes of Health
Yang Chen: National Institutes of Health
Eunhye Lee: National Institutes of Health
Jeong Kyu Bang: Korea Basic Science Institute
Jung Mi Lim: National Institutes of Health
Rodolfo Ghirlando: National Institutes of Health
Lixin Fan: Frederick National Laboratory for Cancer Research
Yun-Xing Wang: National Institutes of Health
Bo Yeon Kim: Korea Research Institute of Bioscience and Biotechnology
Jung-Eun Park: National Institutes of Health
Kyung S. Lee: National Institutes of Health

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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 α-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.

Date: 2019
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DOI: 10.1038/s41467-019-08838-2

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