Centrioles, the major component of animal centrosomes, are conserved cell organelles that duplicate once per cell cycle in order to maintain their number. Abnormalities in the centriole duplication process can lead to disease, including primary microcephaly and cancer in humans. At the same time, centrioles are very large (~400x200nm in humans) protein assemblies that seem to have few distinct structural components (SAS-6, STIL, CPAP, Cep135 and microtubules in humans). It is thus both important and intriguing to understand how centrioles form, and what are the mechanistic roles of their components. In this effort we are joined by the groups of Profs. Pierre Gönczy (cell biology, EPFL, Switzerland) and Michel Steinmetz (biophysics of microtubules, Paul Scherrer Institute, Switzerland).

SAS-6 forms oligomers at the core of centrioles that determine the overall 9-fold symmetry of this organelle. Using a combination of X-ray crystallography and electron microscopy we have distinguish two different oligomeric forms of SAS-6. The first, a 9-fold symmetric ring was resolved from Chlamydomonas reinhardtii but appears common in most organisms. The second, a 9-fold symmetric double spiral, appears restricted to the nematode worms. However, whether as spirals or rings, SAS-6 has the same function of forming an initial framework for subsequent centriole components.

"Ring or spiral? Chlamydomonas reinhardtii SAS-6 forms rings in vitro (top: electron micrograph on left, crystallographic model on right), whereas SAS-6 from Caenorhabditis elegans forms long spiral structures (bottom: top: electron micrograph on left, crystallographic model on right)."


Recent studies have shed light on what other centriole proteins may look like. Crystallographic studies of CPAP showed that it adopts a unique domain fold, with periodicity that matches that of tubulin in microtubules. We postulate that fibrils of CPAP may provide a molecular ruler for elongating centrioles.


SAS-5, the nematode equivalent of STIL, showed on the other hand a complex arrangement comprising two oligomerisation domains. Overall SAS-5 is a hexamer, and we believe it may form a seeding point from where SAS-6 oligomers emanate.


Relevant publications:

Cutts EE, Inglis A, Stansfeld PJ, Vakonakis I, Hatzopoulos GN (2016) The centriolar protein CPAP G-box: an amyloid fibril in a single domain. Biochem Soc Trans 43, 838-43.

Rogala KB, Dynes NJ, Hatzopoulos GN, Yan J, Pong SK, Robinson CV, Deane CM, Gönczy P, Vakonakis I (2015) The Caenorhabditis elegans protein SAS-5 forms large oligomeric assemblies critical for centriole formation. eLife 4, 10.7554/eLife.07410.

Hatzopoulos GN, Erat MC, Cutts E, Rogala KB, Slater LM, Stansfeld PJ, Vakonakis I (2013) Structural analysis of the G-box domain of the microcephaly protein CPAP suggests a role in centriole architecture. Structure 21, 2069-77.

Hilbert M, Erat MC, Hachet V, Guichard P, Blank ID, Flückiger I, Slater L, Lowe ED, Hatzopoulos GN, Steinmetz MO, Gönczy P, Vakonakis I (2013) The Caenorhabditis elegans centriolar protein SAS-6 can form a spiral that is consistent with imparting a 9-fold symmetry. Proc. Natl. Acad. Sci. U.S.A. 110, 11373-8.

Kitagawa D, Vakonakis I, Olieric N, Hilbert M, Keller D, Olieric V, Bortfeld M, Erat MC, Flückiger I, Gönczy P, Steinmetz MO (2011) Structural Basis of the 9-Fold Symmetry of Centrioles. Cell. 144, 364-75.



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