1UMW: Structure Of A Human Plk1 Polo-box Domain/phosphopeptide Complex

Citation:
Abstract
Polo-like kinases (Plks) perform crucial functions in cell-cycle progression and multiple stages of mitosis. Plks are characterized by a C-terminal noncatalytic region containing two tandem Polo boxes, termed the Polo-box domain (PBD), which has recently been implicated in phosphodependent substrate targeting. We show that the PBDs of human, Xenopus, and yeast Plks all recognize similar phosphoserine/threonine-containing motifs. The 1.9 A X-ray structure of a human Plk1 PBD-phosphopeptide complex shows that the Polo boxes each comprise beta6alpha structures that associate to form a 12-stranded beta sandwich domain. The phosphopeptide binds along a conserved, positively charged cleft located at the edge of the Polo-box interface. Mutations that specifically disrupt phosphodependent interactions abolish cell-cycle-dependent localization and provide compelling phenotypic evidence that PBD-phospholigand binding is necessary for proper mitotic progression. In addition, phosphopeptide binding to the PBD stimulates kinase activity in full-length Plk1, suggesting a conformational switching mechanism for Plk regulation and a dual functionality for the PBD.
PDB ID: 1UMWDownload
MMDB ID: 25161
PDB Deposition Date: 2003/8/29
Updated in MMDB: 2003/11
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 1UMW: dimeric; determined by author and by software (PQS)
Molecular Components in 1UMW
Label Count Molecule
Proteins (2 molecules)
1
Serine/threonine-protein Kinase PLK(Gene symbol: PLK1)
Molecule annotation
1
Peptide
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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