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1ka6

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(New page: 200px<br /> <applet load="1ka6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ka6" /> '''SAP/SH2D1A bound to peptide n-pY'''<br /> ...)
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[[Image:1ka6.gif|left|200px]]<br />
 
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<applet load="1ka6" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ka6" />
 
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'''SAP/SH2D1A bound to peptide n-pY'''<br />
 
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==Overview==
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==SAP/SH2D1A bound to peptide n-pY==
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The SH2 domain protein SAP/SH2D1A, encoded by the X-linked, lymphoproliferative (XLP) syndrome gene, associates with the hematopoietic, cell surface receptor SLAM in a phosphorylation-independent manner. By, screening a repertoire of synthetic peptides, the specificity of, SAP/SH2D1A has been mapped and a consensus sequence motif for binding, identified, T/S-x-x-x-x-V/I, where x represents any amino acid., Remarkably, this motif contains neither a Tyr nor a pTyr residue, a, hallmark of conventional SH2 domain-ligand interactions. The structures of, the protein, determined by NMR, in complex with two distinct peptides, provide direct evidence in support of a "three-pronged" binding mechanism, for the SAP/SH2D1A SH2 domain in contrast to the "two-pronged" binding for, conventional SH2 domains. Differences in the structures of the two, complexes suggest considerable flexibility in the SH2 domain, as further, confirmed and characterized by hydrogen exchange studies. The structures, also explain binding defects observed in disease-causing SAP/SH2D1A, mutants and suggest that phosphorylation-independent interactions mediated, by SAP/SH2D1A likely play an important role in the pathogenesis of XLP.
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<StructureSection load='1ka6' size='340' side='right'caption='[[1ka6]]' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1ka6]] 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=1KA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KA6 FirstGlance]. <br>
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Known diseases associated with this structure: Amyloidosis, secondary, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104770 104770]], Lymphoproliferative syndrome, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300490 300490]]
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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=NH2:AMINO+GROUP'>NH2</scene>, <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=1ka6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ka6 OCA], [https://pdbe.org/1ka6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ka6 RCSB], [https://www.ebi.ac.uk/pdbsum/1ka6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ka6 ProSAT]</span></td></tr>
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1KA6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KA6 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/SH21A_HUMAN SH21A_HUMAN] Defects in SH2D1A are a cause of lymphoproliferative syndrome X-linked type 1 (XLP1) [MIM:[https://omim.org/entry/308240 308240]; also known as X-linked lymphoproliferative disease (XLPD) or Duncan disease. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.<ref>PMID:11477068</ref> <ref>PMID:9771704</ref> <ref>PMID:11823424</ref> <ref>PMID:10598819</ref> <ref>PMID:11049992</ref> <ref>PMID:11034354</ref> <ref>PMID:11493483</ref> <ref>PMID:14674764</ref> <ref>PMID:15841490</ref> <ref>PMID:16720617</ref>
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A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome., Hwang PM, Li C, Morra M, Lillywhite J, Muhandiram DR, Gertler F, Terhorst C, Kay LE, Pawson T, Forman-Kay JD, Li SC, EMBO J. 2002 Feb 1;21(3):314-23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11823424 11823424]
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== Function ==
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[https://www.uniprot.org/uniprot/SH21A_HUMAN SH21A_HUMAN] Inhibitor of the SLAM self-association. Acts by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. Mediates interaction between FYN and SLAMF1. May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ka/1ka6_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1ka6 ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Forman-Kay, J.]]
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[[Category: Forman-Kay J]]
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[[Category: Gertler, F.]]
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[[Category: Gertler F]]
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[[Category: Hwang, P.M.]]
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[[Category: Hwang PM]]
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[[Category: Kay, L.E.]]
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[[Category: Kay LE]]
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[[Category: Li, C.]]
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[[Category: Li C]]
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[[Category: Li, S.C.]]
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[[Category: Li S-C]]
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[[Category: Lillywhite, J.]]
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[[Category: Lillywhite J]]
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[[Category: Morra, M.]]
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[[Category: Morra M]]
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[[Category: Pawson, T.]]
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[[Category: Pawson T]]
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[[Category: Terhorst, C.]]
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[[Category: Terhorst C]]
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[[Category: NH2]]
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[[Category: protein-peptide complex]]
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[[Category: sh2 domain]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:49:03 2007''
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Current revision

SAP/SH2D1A bound to peptide n-pY

PDB ID 1ka6

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