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1irs

From Proteopedia

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[[Image:1irs.gif|left|200px]]<br /><applet load="1irs" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1irs" />
 
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'''IRS-1 PTB DOMAIN COMPLEXED WITH A IL-4 RECEPTOR PHOSPHOPEPTIDE, NMR, MINIMIZED AVERAGE STRUCTURE'''<br />
 
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==Overview==
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==IRS-1 PTB DOMAIN COMPLEXED WITH A IL-4 RECEPTOR PHOSPHOPEPTIDE, NMR, MINIMIZED AVERAGE STRUCTURE==
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We present the NMR structure of the PTB domain of insulin receptor substrate-1 (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the IL-4 receptor. Despite the lack of sequence homology and different binding specificity, the overall fold of the protein is similar to that of the Shc PTB domain and closely resembles that of PH domains. However, the PTB domain of IRS-1 is smaller than that of Shc (110 versus 170 residues) and binds to phosphopeptides in a distinct manner. We explain the phosphopeptide binding specificity based on the structure of the complex and results of site-directed mutagenesis experiments.
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<StructureSection load='1irs' size='340' side='right'caption='[[1irs]]' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1irs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IRS FirstGlance]. <br>
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Known diseases associated with this structure: AIDS, slow progression to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147781 147781]], Atopy, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147781 147781]], Coronary artery disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147545 147545]], Diabetes mellitus, noninsulin-dependent OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147545 147545]]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
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==About this Structure==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1irs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1irs OCA], [https://pdbe.org/1irs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1irs RCSB], [https://www.ebi.ac.uk/pdbsum/1irs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1irs ProSAT]</span></td></tr>
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1IRS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IRS OCA].
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</table>
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== Disease ==
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==Reference==
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[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN] Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[https://omim.org/entry/125853 125853].<ref>PMID:14707024</ref> <ref>PMID:8723689</ref> <ref>PMID:10206679</ref> <ref>PMID:12843189</ref> <ref>PMID:15590636</ref>
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Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain., Zhou MM, Huang B, Olejniczak ET, Meadows RP, Shuker SB, Miyazaki M, Trub T, Shoelson SE, Fesik SW, Nat Struct Biol. 1996 Apr;3(4):388-93. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8599766 8599766]
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== Function ==
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[[Category: Escherichia coli]]
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[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN] May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).<ref>PMID:16878150</ref> <ref>PMID:14707024</ref>
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[[Category: Protein complex]]
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== Evolutionary Conservation ==
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[[Category: Feisk, S W.]]
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[[Image:Consurf_key_small.gif|200px|right]]
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[[Category: Huang, B.]]
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Check<jmol>
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[[Category: Meadows, R P.]]
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<jmolCheckbox>
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[[Category: Miyazaki, M.]]
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ir/1irs_consurf.spt"</scriptWhenChecked>
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[[Category: Olejniczak, E T.]]
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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[[Category: Shoelson, S E.]]
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<text>to colour the structure by Evolutionary Conservation</text>
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[[Category: Shuker, S B.]]
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</jmolCheckbox>
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[[Category: Trub, T.]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1irs ConSurf].
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[[Category: Zhou, M M.]]
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<div style="clear:both"></div>
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[[Category: complex]]
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== References ==
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[[Category: complex (signal transduction/peptide)]]
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<references/>
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[[Category: phosphotyrosine binding domain (ptb)]]
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__TOC__
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[[Category: signal transduction]]
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</StructureSection>
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[[Category: Homo sapiens]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:14:55 2008''
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[[Category: Large Structures]]
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[[Category: Feisk SW]]
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[[Category: Huang B]]
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[[Category: Meadows RP]]
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[[Category: Miyazaki M]]
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[[Category: Olejniczak ET]]
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[[Category: Shoelson SE]]
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[[Category: Shuker SB]]
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[[Category: Trub T]]
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[[Category: Zhou M-M]]

Current revision

IRS-1 PTB DOMAIN COMPLEXED WITH A IL-4 RECEPTOR PHOSPHOPEPTIDE, NMR, MINIMIZED AVERAGE STRUCTURE

PDB ID 1irs

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