Fig. 8: Schematics illustrating the stepwise self-assembly processes and the effect of misorganizing the Cep63•Cep152 platform on the Plk4-mediated centriole duplication, the abnormalities of which could lead to the development of various human diseases, including cancer.
a In a concentration-dependent manner, the Cep63 (424–541)•Cep152 (1205–1295) heterotetramer generates octameric and hexadecameric complexes, leading to the formation of a cylindrical self-assembly. iSCAMS was used to determine the Kd value for forming the heterotetrameric building block, while the Kd values for tetramer–octamer and octamer–hexadecamer equilibria were determined from sedimentation equilibrium analyses (Fig. 2d). Formation of the heterotetrameric building block is presumably almost irreversible (dotted arrow), hardly dissociating its components under various conditions. Cylindrical self-assemblies are very stable12. The two Cep152 mutants either lacking the (1205–1295) region (∆23) or containing the I1279D, L1286D mutations (2D) fail to form the heterotetrameric building block and a higher-order self-assembly. b Cep152 WT, which localizes within a defined region of the PCM space, properly recruits and promotes Plk4-dependent centriole duplication and cell proliferation. In contrast, its respective ∆23 and 2D mutants misorganize their pericentriolar platform, displaying a broader distribution and lower density of the Plk4-binding Cep152 N-terminus (see text for details). Consequently, these mutants fail to properly promote Plk4’s ring-to-dot conversion and centriole duplication. This defect could ultimately lead to various human disorders.
