The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication

• Published in: Structure (London) 2012-11, Vol.20 (11), p.1905-1917
• Main Authors: Slevin, Lauren K., Nye, Jonathan, Pinkerton, Derek C., Buster, Daniel W., Rogers, Gregory C., Slep, Kevin C.
• Format: Article
• Language: English
• Subjects: Architecture; Binding; Cassettes; Centrioles; Constraining; Crystal structure; Crystallography, X-Ray; Humans; Kinases; Models, Molecular; Polarity; Protein Conformation; Protein-Serine-Threonine Kinases - chemistry; Reproduction
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2012.08.025

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. [Display omitted] ► The Plk4 cryptic polo box is a structurally unique, tandem polo box array: PB1-PB2 ► Full length Plk4 comprises three polo box domains, a unique polo kinase architecture ► The Plk4 PB1-PB2 cassette is required for Asterless binding and centriole targeting ► The Plk4 PB1-PB2 homodimer potentiates Plk4 degradation Polo like kinase 4 (Plk4) is a centriole duplication factor that localizes to centrioles via the Cryptic Polo Box (PB) domain. Slevin et al. present the structure of this domain, revealing asymmetric PB1-PB2 homodimer, required for centriole targeting and trans-autophosphorylation that primes Plk4 for degradation.