title: The structure of the plk4 cryptic polo box reveals two tandem polo boxes required for centriole duplication.
abstract: Centrioles are key microtubule polarity determinants. Centriole duplication is tightly controlled to prevent cells from developing multipolar spindles, a situation that promotes chromosomal instability. A conserved component in the duplication pathway is Plk4, a polo kinase family member that localizes to centrioles in M/G1. To limit centriole duplication, Plk4 levels are controlled through trans-autophosphorylation that primes ubiquitination. In contrast to Plks 1-3, Plk4 possesses a unique central region called the "cryptic polo box." Here, we present the crystal structure of this region at 2.3 Å resolution. Surprisingly, the structure reveals two tandem homodimerized polo boxes, PB1-PB2, that form a unique winged architecture. The full PB1-PB2 cassette is required for binding the centriolar protein Asterless as well as robust centriole targeting. Thus, with its C-terminal polo box (PB3), Plk4 has a triple polo box architecture that facilitates oligomerization, targeting, and promotes trans-autophosphorylation, limiting centriole duplication to once per cell cycle.
authors.affiliation: Department of Biology, CB 3280, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Slevin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Nye
authors.forename: Derek C
authors.initials: DC
authors.lastname: Pinkerton
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Buster
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Rogers
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Slep
mesh_terms: D002502:Centrioles; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*
chemical_list: C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases