1umw
From Proteopedia
(New page: 200px<br /> <applet load="1umw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1umw, resolution 1.90Å" /> '''STRUCTURE OF A HUMA...) |
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| - | [[Image:1umw.gif|left|200px]]<br /> | + | [[Image:1umw.gif|left|200px]]<br /><applet load="1umw" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1umw" size=" | + | |
caption="1umw, resolution 1.90Å" /> | caption="1umw, resolution 1.90Å" /> | ||
'''STRUCTURE OF A HUMAN PLK1 POLO-BOX DOMAIN/PHOSPHOPEPTIDE COMPLEX'''<br /> | '''STRUCTURE OF A HUMAN PLK1 POLO-BOX DOMAIN/PHOSPHOPEPTIDE COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Polo-like kinases (Plks) perform crucial functions in cell-cycle | + | 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== | ==About this Structure== | ||
| - | 1UMW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1UMW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UMW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Elia, A.]] | [[Category: Elia, A.]] | ||
[[Category: Rellos, P.]] | [[Category: Rellos, P.]] | ||
| - | [[Category: Smerdon, S | + | [[Category: Smerdon, S J.]] |
| - | [[Category: Yaffe, M | + | [[Category: Yaffe, M B.]] |
[[Category: kinase]] | [[Category: kinase]] | ||
[[Category: phosphopeptide-binding domain]] | [[Category: phosphopeptide-binding domain]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:26:14 2008'' |
Revision as of 13:26, 21 February 2008
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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
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