The Caenorhabditis elegans protein SAS-5 forms large oligomeric assemblies critical for centriole formation

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Abstract

Centrioles are microtubule-based organelles crucial for cell division, sensing and motility. In C. elegans, the onset of centriole formation requires notably the proteins SAS-5 and SAS-6, which have functional homologs 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.

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Kacper B Rogala

Department of Biochemistry, University of Oxford, Oxford, United Kingdom

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The authors declare that no competing interests exist.
Nicola J Dynes

Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland

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The authors declare that no competing interests exist.
Georgios N Hatzopoulos

Department of Biochemistry, University of Oxford, Oxford, United Kingdom

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The authors declare that no competing interests exist.
Jun Yan

Department of Chemistry, University of Oxford, Oxford, United Kingdom

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The authors declare that no competing interests exist.
Sheng Kai Pong

Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland

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The authors declare that no competing interests exist.
Carol V Robinson

Department of Chemistry, University of Oxford, Oxford, United Kingdom

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The authors declare that no competing interests exist.
Charlotte M Deane

Department of Statistics, University of Oxford, Oxford, United Kingdom

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The authors declare that no competing interests exist.
Pierre Gönczy

Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland

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The authors declare that no competing interests exist.
Ioannis Vakonakis

Department of Biochemistry, University of Oxford, Oxford, United Kingdom

For correspondence
ioannis.vakonakis@bioch.ox.ac.uk

Competing interests
The authors declare that no competing interests exist.

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