1w1d

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{{STRUCTURE_1w1d| PDB=1w1d | SCENE= }}
{{STRUCTURE_1w1d| PDB=1w1d | SCENE= }}
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'''CRYSTAL STRUCTURE OF THE PDK1 PLECKSTRIN HOMOLOGY (PH) DOMAIN BOUND TO INOSITOL (1,3,4,5)-TETRAKISPHOSPHATE'''
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===CRYSTAL STRUCTURE OF THE PDK1 PLECKSTRIN HOMOLOGY (PH) DOMAIN BOUND TO INOSITOL (1,3,4,5)-TETRAKISPHOSPHATE===
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==Overview==
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3-phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates and activates many kinases belonging to the AGC subfamily. PDK1 possesses a C-terminal pleckstrin homology (PH) domain that interacts with PtdIns(3,4,5)P3/PtdIns(3,4)P2 and with lower affinity to PtdIns(4,5)P2. We describe the crystal structure of the PDK1 PH domain, in the absence and presence of PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4. The structures reveal a 'budded' PH domain fold, possessing an N-terminal extension forming an integral part of the overall fold, and display an unusually spacious ligand-binding site. Mutagenesis and lipid-binding studies were used to define the contribution of residues involved in phosphoinositide binding. Using a novel quantitative binding assay, we found that Ins(1,3,4,5,6)P5 and InsP6, which are present at micromolar levels in the cytosol, interact with full-length PDK1 with nanomolar affinities. Utilising the isolated PDK1 PH domain, which has reduced affinity for Ins(1,3,4,5,6)P5/InsP6, we perform localisation studies that suggest that these inositol phosphates serve to anchor a portion of cellular PDK1 in the cytosol, where it could activate its substrates such as p70 S6-kinase and p90 ribosomal S6 kinase that do not interact with phosphoinositides.
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{{ABSTRACT_PUBMED_15457207}}
==About this Structure==
==About this Structure==
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[[Category: Serine/threonine protein kinase]]
[[Category: Serine/threonine protein kinase]]
[[Category: Signal transduction]]
[[Category: Signal transduction]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:01:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:36:12 2008''

Revision as of 11:36, 28 July 2008

Image:1w1d.png

Template:STRUCTURE 1w1d

CRYSTAL STRUCTURE OF THE PDK1 PLECKSTRIN HOMOLOGY (PH) DOMAIN BOUND TO INOSITOL (1,3,4,5)-TETRAKISPHOSPHATE

Template:ABSTRACT PUBMED 15457207

About this Structure

1W1D is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates., Komander D, Fairservice A, Deak M, Kular GS, Prescott AR, Peter Downes C, Safrany ST, Alessi DR, van Aalten DM, EMBO J. 2004 Oct 13;23(20):3918-28. Epub 2004 Sep 30. PMID:15457207

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