Kantsadi, Anastassia L.Hatzopoulos, Georgios N.Gonczy, PierreVakonakis, Ioannis2022-06-062022-06-062022-06-062022-05-0510.1016/j.str.2022.02.005https://infoscience.epfl.ch/handle/20.500.14299/188312WOS:000799220200004Centrioles are eukaryotic organelles that template the formation of cilia and flagella, as well as organize the microtubule network and the mitotic spindle in animal cells. Centrioles have proximal-distal polarity and a 9 fold radial symmetry imparted by a likewise symmetrical central scaffold, the cartwheel. The spindle assembly abnormal protein 6 (SAS-6) self-assembles into 9-fold radially symmetric ring-shaped oligomers that stack via an unknown mechanism to form the cartwheel. Here, we uncover a homo-oligomerization interaction mediated by the coiled-coil domain of SAS-6. Crystallographic structures of Chlamydomonas reinhardtii SAS-6 coiled-coil complexes suggest this interaction is asymmetric, thereby imparting polarity to the cartwheel. Using a cryoelectron microscopy (cryo-EM) reconstitution assay, we demonstrate that amino acid substitutions disrupting this asymmetric association also impair SAS-6 ring stacking. Our work raises the possibility that the asymmetric interaction inherent to SAS-6 coiled-coil provides a polar element for cartwheel assembly, which may assist the establishment of the centriolar proximal-distal axis.Biochemistry & Molecular BiologyBiophysicsCell Biologycentrosome duplication9-fold symmetryproteinprocentrioleelegansciliaarchitectureintegrationfeaturessuggesttext::journal::journal article::research article