Molecular architecture of a cylindrical self-assembly at human centrosomes

Nat Commun. 2019 Mar 11;10(1):1151. doi: 10.1038/s41467-019-08838-2.

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.

Publication types

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

MeSH terms

  • Amino Acid Motifs / genetics
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / isolation & purification
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Centrioles / metabolism*
  • Crystallography, X-Ray
  • HEK293 Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Microscopy, Fluorescence
  • Mutation
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / isolation & purification
  • Neoplasm Proteins / metabolism*
  • Protein Conformation, alpha-Helical
  • Protein Multimerization / physiology*
  • Protein Serine-Threonine Kinases / isolation & purification
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Time-Lapse Imaging

Substances

  • CEP152 protein, human
  • CEP63 protein, human
  • Cell Cycle Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • PLK4 protein, human
  • Protein Serine-Threonine Kinases