Computational support for a scaffolding mechanism of centriole assembly.
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.
Institute for Theoretical Physics and BioQuant, Heidelberg University, D-69120 Heidelberg, Germany.
Heinrich C R
HC
Klein
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Paul
P
Guichard
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Virginie
V
Hamel
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Pierre
P
Gönczy
Institute for Theoretical Physics and BioQuant, Heidelberg University, D-69120 Heidelberg, Germany.
Ulrich S
US
Schwarz
D018797:Cell Cycle Proteins / Q000737:chemistry; D002502:Centrioles / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
D018797:Cell Cycle Proteins; C497202:SASS6 protein, human