1UMW

Structure of a human Plk1 Polo-box domain/phosphopeptide complex

Summary for 1UMW

• Entry DOI: 10.2210/pdb1umw/pdb
• Descriptor: SERINE/THREONINE-PROTEIN KINASE PLK, PEPTIDE (3 entities in total)
• Functional Keywords: kinase, phosphopeptide-binding domain, transferase
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: P53350
• Total number of polymer chains: 4
• Total formula weight: 56250.00

Authors

Rellos, P.,Elia, A.,Yaffe, M.B.,Smerdon, S.J. (deposition date: 2003-08-29, release date: 2003-10-16, Last modification date: 2024-11-20)

Primary citation

Elia, A.,Rellos, P.,Haire, L.,Chao, J.,Ivins, F.,Hoepker, K.,Mohammad, D.,Cantley, L.,Smerdon, S.J.,Yaffe, M.B.
The Molecular Basis for Phosphodependent Substrate Targeting and Regulation of Plks by the Polo-Box Domain
Cell(Cambridge,Mass.), 115:83-, 2003

PubMed 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.

PubMed: 14532005
DOI: 10.1016/S0092-8674(03)00725-6

Experimental method

X-RAY DIFFRACTION (1.9 Å)