Abstract
Centrioles are essential for forming cilia, flagella and centrosomes. Successful centriole assembly requires proteins of the SAS-6 family, which can form oligomeric ring structures with ninefold symmetry in vitro. While important progress has been made in understanding SAS-6 protein biophysics, the mechanisms enabling ring formation in vivo remain elusive. Likewise, the mechanisms by which a nascent centriole forms near-orthogonal to an existing one are not known. Here, we investigate possible mechanisms of centriole assembly using coarse-grained Brownian dynamics computer simulations in combination with a rate equation approach. Our results suggest that without any external factors, strong stabilization associated with ring closure would be needed to enable efficient ring formation. Strikingly, our simulations reveal that a scaffold-assisted assembly mechanism can trigger robust ring formation owing to local cooperativity, and that this mechanism can also impart orthogonalilty to centriole assembly. Overall, our findings provide novel insights into the organizing principles governing the assembly of this important organelle.
Highlights
Supramolecular protein complexes are central to many cellular processes[1,2]
The characteristic ninefold radial symmetry of centrioles stems in most systems from the so-called cartwheel, which consists of several rings with a central hub ~23 nm in diameter, from which nine spokes point radially outwards[9,15,16,17]
Previous analytical ultra-centrifugation (AUC) experiments performed with bacterially expressed CrSAS-6-6HR at a concentration of c = 75 μM suggest that at steady state, mainly two or three homodimers are present in higher order assemblies (Fig. S4 of reference22)
Summary
Supramolecular protein complexes are central to many cellular processes[1,2]. understanding the mechanisms governing their coordinated assembly in a given cellular location and at the proper time is a fundamental pursuit in biology[3]. Nine homodimers of SAS-6 proteins can assemble in vitro into ring-like structures that resemble the central hub of the cartwheel[17,22,24,25,26], suggesting that proteins of the SAS-6 family act as a nucleus for the assembly process and dictate the signature ninefold symmetry of the entire centriole. While aspects of the structure and the bimolecular interactions of SAS-6 proteins have been extensively investigated, the mechanisms enabling the assembly of complete rings at physiological concentrations remain elusive. Our main results are that physiological concentrations of SAS-6 make ring formation very unlikely and that scaffold-assisted mechanisms might be used in cells to ensure centriole assembly. Our computational analysis suggests a simple geometrical mechanism to explain near-orthogonality of centriole assembly
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
