POLO-Box Domain
Class:Phospho-Ser binding


No ImageThe polo-box domain consists of two polo-box regions (PB1 and 2).  Together, the two polo-box regions form a 12-stranded beta sandwich flanked by three alpha-helical segments. PB1 and PB2 share a similar fold with each being comprised of a six-stranded antiparallel β-sheet shielded by one α-helix, even though they exhibit only 12% sequence identity. The phosphopeptide binds in a cleft between the two polo-box regions and interacts with beta1 from PB1, the N-terminal end of L2 and beta8/9 from PB2. The only residues that interact with the phosphate group are His-538 and Lys-540 from PB2. These phosphopeptide interacting residues are highly conserved in the polo like kinases, suggesting a conserved ability to bind phosphopeptide motifs across all family members.  

Structure Reference:
Cheng, K.Y. et al. (2003) EMBO J. 22(21): 5757-5768. PDB: 1Q4K.
Elia, A. et al. (2003) Cell. 115(1): 83-95.

Domain binding and function:
The Polo-Box domain is exclusively found in the family of Polo-like kinases that regulate mitotic entry, spindle assembly, centrosome maturation, chromosome segregation, cytokinesis and cell cycle arrest. The approximately 200 amino acid Polo-Box domain consists of two highly conserved Polo Box motifs of ~70-80 amino acids each, and is positioned C-terminal to an N-terminal Ser/Thr kinase domain. The Polo-Box domain performs dual roles, determining subcellular localization and autoinhibitory regulation of the kinase domain.  The Polo-Box module, consisting of two Polo-Box motifs, the region between them, and a portion of the linker between the end of the kinase domain and the first Polo-Box, functions to recognize phosphopeptides with the core consensus motif Ser-pThr/pSer-Pro/X.  Furthermore, PLK1 is overexpressed in a broad range of human tumours indicating its involvement in carcinogenesis. 
Examples of Proteins: 
POLO like kinase
Binding Partner
Plk1Cdc25C, Chk2, Mcm7, GRASP65

Consensus Binding Sites