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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'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15457207}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15457207 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15457207}} |
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| ==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]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:01:13 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:36:12 2008'' |
