POLO-Box Domain
Class:Phospho-Ser binding

Structure:

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
[Pro/Phe]-[Φ/Pro]-[Φ/Ala/Gln]-[Thr/Gln/His/Met]-Ser-[pThr/pSer]-[Pro/X]
Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors: Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada