title: Structure of the C. elegans ZYG-1 cryptic polo box suggests a conserved mechanism for centriolar docking of Plk4 kinases.
abstract: Plk4 family kinases control centriole assembly. Plk4s target mother centrioles through an interaction between their cryptic polo box (CPB) and acidic regions in the centriolar receptors SPD-2/Cep192 and/or Asterless/Cep152. Here, we report a crystal structure for the CPB of C. elegans ZYG-1, which forms a Z-shaped dimer containing an intermolecular β sheet with an extended basic surface patch. Biochemical and in vivo analysis revealed that electrostatic interactions dock the ZYG-1 CPB basic patch onto the SPD-2-derived acidic region to promote ZYG-1 targeting and new centriole assembly. Analysis of a different crystal form of the Drosophila Plk4 (DmPlk4) CPB suggests that it also forms a Z-shaped dimer. Comparison of the ZYG-1 and DmPlk4 CPBs revealed structural changes in the ZYG-1 CPB that confer selectivity for binding SPD-2 over Asterless-derived acidic regions. Overall, our findings suggest a conserved mechanism for centriolar docking of Plk4 homologs that initiate daughter centriole assembly.
authors: Max F. Perutz Laboratories, Medical University of Vienna, 1030 Vienna, Austria.
authors: Ekaterina
authors: E
authors: Shimanovskaya
authors: Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Valeria
authors: V
authors: Viscardi
authors: Max F. Perutz Laboratories, Medical University of Vienna, 1030 Vienna, Austria.
authors: Johannes
authors: J
authors: Lesigang
authors: Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
authors: Molly M
authors: MM
authors: Lettman
authors: Max F. Perutz Laboratories, Medical University of Vienna, 1030 Vienna, Austria.
authors: Renping
authors: R
authors: Qiao
authors: European Molecular Biology Laboratory, Hamburg Unit, EMBL c/o DESY, Notkestrasse 85, 22603 Hamburg, Germany.
authors: Dmitri I
authors: DI
authors: Svergun
authors: European Molecular Biology Laboratory, Grenoble Outstation, 6 rue Jules Horowitz, 38042 Grenoble, France; Unit for Virus Host-Cell Interactions, University Grenoble Alpes-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France.
authors: Adam
authors: A
authors: Round
authors: Department of Cellular and Molecular Medicine, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: koegema@ucsd.edu.
authors: Karen
authors: K
authors: Oegema
authors: Max F. Perutz Laboratories, Medical University of Vienna, 1030 Vienna, Austria. Electronic address: gang.dong@meduniwien.ac.at.
authors: Gang
authors: G
authors: Dong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism / Q000502:physiology*; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D029742:Caenorhabditis elegans Proteins; C486131:SPD-2 protein, C elegans; D011494:Protein Kinases; C429649:zyg-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases