Molecular architecture of a cylindrical self-assembly at human centrosomes.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
11 03 2019
Historique:
received: 23 05 2018
accepted: 01 02 2019
entrez: 13 3 2019
pubmed: 13 3 2019
medline: 6 4 2019
Statut: epublish

Résumé

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.

Identifiants

pubmed: 30858376
doi: 10.1038/s41467-019-08838-2
pii: 10.1038/s41467-019-08838-2
pmc: PMC6411776
doi:

Substances chimiques

CEP152 protein, human 0
CEP63 protein, human 0
Cell Cycle Proteins 0
Neoplasm Proteins 0
RNA, Small Interfering 0
Recombinant Proteins 0
PLK4 protein, human EC 2.7.1.-
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Video-Audio Media

Langues

eng

Sous-ensembles de citation

IM

Pagination

1151

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Auteurs

Tae-Sung Kim (TS)

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Liang Zhang (L)

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Jong Il Ahn (J)

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Lingjun Meng (L)

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Yang Chen (Y)

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Eunhye Lee (E)

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Jeong Kyu Bang (JK)

Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Republic of Korea.

Jung Mi Lim (JM)

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Rodolfo Ghirlando (R)

Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Lixin Fan (L)

Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.

Yun-Xing Wang (YX)

Structural Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.

Bo Yeon Kim (BY)

Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.

Jung-Eun Park (JE)

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Kyung S Lee (KS)

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. kyunglee@mail.nih.gov.

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Classifications MeSH