KCS

Polo-like kinases (Plks) are serine/threonine kinases that regulate cell cycle, which commonly contain a canonical catalytic domain and a unique polo-box domain. Polo-like kinase 4 (Plk4) is a master regulator of centriole duplication, whose proper recruitment to centriole is critical for maintaining genomic integrity. The cryptic polo-box domain (CPB) of Plk4 is necessary for the protein function by interacting with the centriolar receptors including Cep152 and Cep192. We found the assembly of Cep152 around the Cep192-encircled daughter centriole and the relocalization of Plk4 from the inner Cep192 ring to the outer Cep152 ring during cell cycle. Crystal structures of the CPB of Plk4 alone and in complex with Cep192- and Cep152-derived fragments revealed that the fragements bind to Plk4 in an opposite orientations and mutually exclusively. Together with the higher binding affinity of Cep152 over Cep192 to Plk4, it accounts for the effective ‘snatching’ of Plk4 from the preformed Plk4-Cep192 complex to the Plk4-Cep152 complex. These results demonstrate that Plk4 is regulated in time and space through ordered interactions of its CPB with two scaffold proteins, Cep192 and Cep152.