1eaz
From Proteopedia
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| - | [[Image:1eaz.gif|left|200px]]<br /><applet load="1eaz" size=" | + | [[Image:1eaz.gif|left|200px]]<br /><applet load="1eaz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1eaz, resolution 1.4Å" /> | caption="1eaz, resolution 1.4Å" /> | ||
'''CRYSTAL STRUCTURE OF THE PHOSPHOINOSITOL (3,4)-BISPHOSPHATE BINDING PH DOMAIN OF TAPP1 FROM HUMAN.'''<br /> | '''CRYSTAL STRUCTURE OF THE PHOSPHOINOSITOL (3,4)-BISPHOSPHATE BINDING PH DOMAIN OF TAPP1 FROM HUMAN.'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1EAZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CIT as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=LBS:Lbs Stands For Lipid Binding Site. Cb Atom Responsible F ...'>LBS</scene>. Full crystallographic information is available from [http:// | + | 1EAZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CIT:'>CIT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=LBS:Lbs+Stands+For+Lipid+Binding+Site.+Cb+Atom+Responsible+F+...'>LBS</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EAZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: signalling]] | [[Category: signalling]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:38:51 2008'' |
Revision as of 07:38, 3 February 2008
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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 with as ligand. Known structural/functional Site: . 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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