1h10: Difference between revisions
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'''HIGH RESOLUTION STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PROTEIN KINASE B/AKT BOUND TO INS(1,3,4,5)-TETRAKISPHOPHATE''' | '''HIGH RESOLUTION STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PROTEIN KINASE B/AKT BOUND TO INS(1,3,4,5)-TETRAKISPHOPHATE''' | ||
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[[Category: Deak, M.]] | [[Category: Deak, M.]] | ||
[[Category: Thomas, C C.]] | [[Category: Thomas, C C.]] | ||
[[Category: | [[Category: Inositol tetrakisphophate]] | ||
[[Category: | [[Category: Phosphoinositide]] | ||
[[Category: | [[Category: Phosphorylation]] | ||
[[Category: | [[Category: Pleckstrin]] | ||
[[Category: | [[Category: Protein kinase b]] | ||
[[Category: | [[Category: Serine/threonine protein kinase]] | ||
[[Category: | [[Category: Signalling protein]] | ||
[[Category: | [[Category: Transferase]] | ||
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Revision as of 18:16, 2 May 2008
HIGH RESOLUTION STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PROTEIN KINASE B/AKT BOUND TO INS(1,3,4,5)-TETRAKISPHOPHATE
OverviewOverview
The products of PI 3-kinase activation, PtdIns(3,4,5)P3 and its immediate breakdown product PtdIns(3,4)P2, trigger physiological processes, by interacting with proteins possessing pleckstrin homology (PH) domains. One of the best characterized PtdIns(3,4,5)P3/PtdIns(3,4)P2 effector proteins is protein kinase B (PKB), also known as Akt. PKB possesses a PH domain located at its N terminus, and this domain binds specifically to PtdIns(3,4,5)P3 and PtdIns(3,4)P2 with similar affinity. Following activation of PI 3-kinase, PKB is recruited to the plasma membrane by virtue of its interaction with PtdIns(3,4,5)P3/PtdIns(3,4)P2. PKB is then activated by the 3-phosphoinositide-dependent pro-tein kinase-1 (PDK1), which like PKB, possesses a PtdIns(3,4,5)P3/PtdIns(3,4)P2 binding PH domain. Here, we describe the high-resolution crystal structure of the isolated PH domain of PKB(alpha) in complex with the head group of PtdIns(3,4,5)P3. The head group has a significantly different orientation and location compared to other Ins(1,3,4,5)P4 binding PH domains. Mutagenesis of the basic residues that form ionic interactions with the D3 and D4 phosphate groups reduces or abolishes the ability of PKB to interact with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The D5 phosphate faces the solvent and forms no significant interactions with any residue on the PH domain, and this explains why PKB interacts with similar affinity with both PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
About this StructureAbout this Structure
1H10 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate., Thomas CC, Deak M, Alessi DR, van Aalten DM, Curr Biol. 2002 Jul 23;12(14):1256-62. PMID:12176338 Page seeded by OCA on Fri May 2 18:16:47 2008