1unp

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{{STRUCTURE_1unp| PDB=1unp | SCENE= }}
{{STRUCTURE_1unp| PDB=1unp | SCENE= }}
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'''CRYSTAL STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PKB ALPHA'''
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===CRYSTAL STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PKB ALPHA===
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==Overview==
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Protein kinase B (PKB/Akt) is a key regulator of cell growth, proliferation and metabolism. It possesses an N-terminal pleckstrin homology (PH) domain that interacts with equal affinity with the second messengers PtdIns(3,4,5)P3 and PtdIns(3,4)P2, generated through insulin and growth factor-mediated activation of phosphoinositide 3-kinase (PI3K). The binding of PKB to PtdIns(3,4,5)P3/PtdIns(3,4)P2 recruits PKB from the cytosol to the plasma membrane and is also thought to induce a conformational change that converts PKB into a substrate that can be activated by the phosphoinositide-dependent kinase 1 (PDK1). In this study we describe two high-resolution crystal structures of the PH domain of PKBalpha in a noncomplexed form and compare this to a new atomic resolution (0.98 A, where 1 A=0.1 nm) structure of the PH domain of PKBalpha complexed to Ins(1,3,4,5)P4, the head group of PtdIns(3,4,5)P3. Remarkably, in contrast to all other PH domains crystallized so far, our data suggest that binding of Ins(1,3,4,5)P4 to the PH domain of PKB, induces a large conformational change. This is characterized by marked changes in certain residues making up the phosphoinositide-binding site, formation of a short a-helix in variable loop 2, and a movement of variable loop 3 away from the lipid-binding site. Solution studies with CD also provided evidence of conformational changes taking place upon binding of Ins(1,3,4,5)P4 to the PH domain of PKB. Our data provides the first structural insight into the mechanism by which the interaction of PKB with PtdIns(3,4,5)P3/PtdIns(3,4)P2 induces conformational changes that could enable PKB to be activated by PDK1.
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(as it appears on PubMed at http://www.pubmed.gov), where 12964941 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12964941}}
==About this Structure==
==About this Structure==
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[[Category: Pleckstrin homology domain]]
[[Category: Pleckstrin homology domain]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:28:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:52:35 2008''

Revision as of 15:52, 27 July 2008

Image:1unp.png

Template:STRUCTURE 1unp

CRYSTAL STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PKB ALPHA

Template:ABSTRACT PUBMED 12964941

About this Structure

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

Reference

Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change., Milburn CC, Deak M, Kelly SM, Price NC, Alessi DR, Van Aalten DM, Biochem J. 2003 Nov 1;375(Pt 3):531-8. PMID:12964941

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