title: The Caenorhabditis elegans protein SAS-5 forms large oligomeric assemblies critical for centriole formation.
abstract: Centrioles are microtubule-based organelles crucial for cell division, sensing and motility. In Caenorhabditis elegans, the onset of centriole formation requires notably the proteins SAS-5 and SAS-6, which have functional equivalents across eukaryotic evolution. Whereas the molecular architecture of SAS-6 and its role in initiating centriole formation are well understood, the mechanisms by which SAS-5 and its relatives function is unclear. Here, we combine biophysical and structural analysis to uncover the architecture of SAS-5 and examine its functional implications in vivo. Our work reveals that two distinct self-associating domains are necessary to form higher-order oligomers of SAS-5: a trimeric coiled coil and a novel globular dimeric Implico domain. Disruption of either domain leads to centriole duplication failure in worm embryos, indicating that large SAS-5 assemblies are necessary for function in vivo.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Kacper B
authors.initials: KB
authors.lastname: Rogala
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Dynes
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Hatzopoulos
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland.
authors.forename: Sheng Kai
authors.initials: SK
authors.lastname: Pong
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
authors.affiliation: Department of Statistics, University of Oxford, Oxford, United Kingdom.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Deane
authors.affiliation: Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gönczy
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vakonakis
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002502:Centrioles / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C488496:SAS-5 protein, C elegans
keywords: C. elegans; biophysics; cell biology; centrioles; crystallography; structural biology; structures