1umw
From Proteopedia
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STRUCTURE OF A HUMAN PLK1 POLO-BOX DOMAIN/PHOSPHOPEPTIDE COMPLEX
Overview
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.
About this Structure
1UMW is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The molecular basis for phosphodependent substrate targeting and regulation of Plks by the Polo-box domain., Elia AE, Rellos P, Haire LF, Chao JW, Ivins FJ, Hoepker K, Mohammad D, Cantley LC, Smerdon SJ, Yaffe MB, Cell. 2003 Oct 3;115(1):83-95. PMID:14532005
Page seeded by OCA on Mon Nov 12 19:36:35 2007
