4g7n
From Proteopedia
The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication
Structural highlights
Function[PLK4_DROME] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the mother centriole cylinder, using mother centriole as a platform, leading to the recruitment of centriole biogenesis proteins such as Sas-6. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Centrosome amplification following overexpression can initiate tumorigenesis, highlighting the importance of centrosome regulation in cancers.[1] [2] [3] Publication Abstract from PubMedCentrioles 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 A 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. The Structure of the Plk4 Cryptic Polo Box Reveals Two Tandem Polo Boxes Required for Centriole Duplication.,Slevin LK, Nye J, Pinkerton DC, Buster DW, Rogers GC, Slep KC Structure. 2012 Sep 18. pii: S0969-2126(12)00328-0. doi:, 10.1016/j.str.2012.08.025. PMID:23000383[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||||
