1eaz
From Proteopedia
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| - | [[Image:1eaz.gif|left|200px]] | + | [[Image:1eaz.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF THE PHOSPHOINOSITOL (3,4)-BISPHOSPHATE BINDING PH DOMAIN OF TAPP1 FROM HUMAN.''' | + | {{Structure |
| + | |PDB= 1eaz |SIZE=350|CAPTION= <scene name='initialview01'>1eaz</scene>, resolution 1.4Å | ||
| + | |SITE= <scene name='pdbsite=LBS:Lbs+Stands+For+Lipid+Binding+Site.+Cb+Atom+Responsible+F+...'>LBS</scene> | ||
| + | |LIGAND= <scene name='pdbligand=CIT:CITRIC ACID'>CIT</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF THE PHOSPHOINOSITOL (3,4)-BISPHOSPHATE BINDING PH DOMAIN OF TAPP1 FROM HUMAN.''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1EAZ is a [ | + | 1EAZ is a [[Single protein]] structure of sequence 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=1EAZ OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity., Thomas CC, Dowler S, Deak M, Alessi DR, van Aalten DM, Biochem J. 2001 Sep 1;358(Pt 2):287-94. PMID:[http:// | + | Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity., Thomas CC, Dowler S, Deak M, Alessi DR, van Aalten DM, Biochem J. 2001 Sep 1;358(Pt 2):287-94. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11513726 11513726] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: signalling]] | [[Category: signalling]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:52:55 2008'' |
Revision as of 08:52, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THE PHOSPHOINOSITOL (3,4)-BISPHOSPHATE BINDING PH DOMAIN OF TAPP1 FROM HUMAN.
Contents |
Overview
Phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] and its immediate breakdown product PtdIns(3,4)P(2) function as second messengers in growth factor- and insulin-induced signalling pathways. One of the ways that these 3-phosphoinositides are known to regulate downstream signalling events is by attracting proteins that possess specific PtdIns-binding pleckstrin homology (PH) domains to the plasma membrane. Many of these proteins, such as protein kinase B, phosphoinositide-dependent kinase 1 and the dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1) interact with both PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2) with similar affinity. Recently, a new PH-domain-containing protein, termed tandem PH-domain-containing protein (TAPP) 1, was described which is the first protein reported to bind PtdIns(3,4)P(2) specifically. Here we describe the crystal structure of the PtdIns(3,4)P(2)-binding PH domain of TAPP1 at 1.4 A (1 A=0.1 nm) resolution in complex with an ordered citrate molecule. The structure is similar to the known structure of the PH domain of DAPP1 around the D-3 and D-4 inositol-phosphate-binding sites. However, a glycine residue adjacent to the D-5 inositol-phosphate-binding site in DAPP1 is substituted for a larger alanine residue in TAPP1, which also induces a conformational change in the neighbouring residues. We show that mutation of this glycine to alanine in DAPP1 converts DAPP1 into a TAPP1-like PH domain that only interacts with PtdIns(3,4)P(2), whereas the alanine to glycine mutation in TAPP1 permits the TAPP1 PH domain to interact with PtdIns(3,4,5)P(3).
Disease
Known diseases associated with this structure: Age-related maculopathy, susceptibility to OMIM:[607772]
About this Structure
1EAZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity., Thomas CC, Dowler S, Deak M, Alessi DR, van Aalten DM, Biochem J. 2001 Sep 1;358(Pt 2):287-94. PMID:11513726
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