The structure of the plk4 cryptic polo box reveals two tandem polo boxes required for centriole duplication

Structure. 2012 Nov 7;20(11):1905-17. doi: 10.1016/j.str.2012.08.025. Epub 2012 Sep 20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Centrioles*
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Protein Conformation
  • Protein-Serine-Threonine Kinases / chemistry*

Substances

  • PLK4 protein, human
  • Protein-Serine-Threonine Kinases