Structural Basis for Mitotic Centrosome Assembly in Flies

Cell. 2017 Jun 1;169(6):1078-1089.e13. doi: 10.1016/j.cell.2017.05.030.


In flies, Centrosomin (Cnn) forms a phosphorylation-dependent scaffold that recruits proteins to the mitotic centrosome, but how Cnn assembles into a scaffold is unclear. We show that scaffold assembly requires conserved leucine zipper (LZ) and Cnn-motif 2 (CM2) domains that co-assemble into a 2:2 complex in vitro. We solve the crystal structure of the LZ:CM2 complex, revealing that both proteins form helical dimers that assemble into an unusual tetramer. A slightly longer version of the LZ can form micron-scale structures with CM2, whose assembly is stimulated by Plk1 phosphorylation in vitro. Mutating individual residues that perturb LZ:CM2 tetramer assembly perturbs the formation of these micron-scale assemblies in vitro and Cnn-scaffold assembly in vivo. Thus, Cnn molecules have an intrinsic ability to form large, LZ:CM2-interaction-dependent assemblies that are critical for mitotic centrosome assembly. These studies provide the first atomic insight into a molecular interaction required for mitotic centrosome assembly.

Keywords: Centrosomin; Cnn; PCM; Plk1; centriole; centrosome; mitosis.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Centrosome / chemistry*
  • Centrosome / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / chemistry
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / metabolism*
  • Homeodomain Proteins / metabolism
  • Mitosis*
  • Models, Molecular
  • Phosphorylation
  • Protein Domains
  • Protein Serine-Threonine Kinases / metabolism
  • Sequence Alignment


  • Drosophila Proteins
  • Homeodomain Proteins
  • cnn protein, Drosophila
  • Protein Serine-Threonine Kinases