1ywo

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(New page: 200px<br /> <applet load="1ywo" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ywo, resolution 1.81&Aring;" /> '''Phospholipase Cgamm...)
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[[Image:1ywo.gif|left|200px]]<br />
 
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<applet load="1ywo" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ywo, resolution 1.81&Aring;" />
 
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'''Phospholipase Cgamma1 SH3 in complex with a SLP-76 motif'''<br />
 
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==Overview==
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==Phospholipase Cgamma1 SH3 in complex with a SLP-76 motif==
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The enzyme phospholipase Cgamma1 (PLCgamma1) is essential for T cell, signaling and activation. Following T cell receptor ligation, PLCgamma1, interacts through its SH2 and SH3 domains with the adaptors LAT and, SLP-76, respectively, to form a multiprotein signaling complex that leads, to activation of PLCgamma1 by Syk tyrosine kinases. To identify the, binding site for PLCgamma1 in SLP-76, we used isothermal titration, calorimetry to measure affinities for the interaction of PLCgamma1-SH3, with a set of overlapping peptides spanning the central proline-rich, region of SLP-76. PLCgamma1-SH3 bound with high specificity to the SLP-76, motif 186PPVPPQRP193, which represents the minimal binding site. To, understand the basis for selective recognition, we determined the crystal, structures of PLCgamma1-SH3 in free form, and bound to a 10-mer peptide, containing this site, to resolutions of 1.60 A and 1.81 A, respectively., The structures reveal that several key contacting residues of the SH3, shift toward the SLP-76 peptide upon complex formation, optimizing the fit, and strengthening hydrophobic interactions. Selectivity results mainly, from strict shape complementarity between protein and peptide, rather than, sequence-specific hydrogen bonding. In addition, Pro193 of SLP-76 assists, in positioning Arg192 into the compass pocket of PLCgamma1-SH3, which, coordinates the compass residue through an unusual aspartate. The, PLCgamma1-SH3/SLP-76 structure provides insights into ligand binding by, SH3 domains related to PLCgamma1-SH3, as well as into recognition by, PLCgamma1 of signaling partners other than SLP-76.
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<StructureSection load='1ywo' size='340' side='right'caption='[[1ywo]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ywo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YWO FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.81&#8491;</td></tr>
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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=1ywo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ywo OCA], [https://pdbe.org/1ywo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ywo RCSB], [https://www.ebi.ac.uk/pdbsum/1ywo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ywo ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PLCG1_RAT PLCG1_RAT] Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration (By similarity).
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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/yw/1ywo_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=1ywo ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1YWO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Active as [http://en.wikipedia.org/wiki/Phosphoinositide_phospholipase_C Phosphoinositide phospholipase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.11 3.1.4.11] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YWO OCA].
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*[[Phospholipase C|Phospholipase C]]
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__TOC__
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==Reference==
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</StructureSection>
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Structural basis for recognition of the T cell adaptor protein SLP-76 by the SH3 domain of phospholipase Cgamma1., Deng L, Velikovsky CA, Swaminathan CP, Cho S, Mariuzza RA, J Mol Biol. 2005 Sep 9;352(1):1-10. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16061254 16061254]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Phosphoinositide phospholipase C]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Cho, S.]]
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[[Category: Cho S]]
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[[Category: Deng, L.]]
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[[Category: Deng L]]
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[[Category: Mariuzza, R.A.]]
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[[Category: Mariuzza RA]]
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[[Category: Swaminathan, C.P.]]
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[[Category: Swaminathan CP]]
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[[Category: Velikovsky, C.A.]]
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[[Category: Velikovsky CA]]
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[[Category: phospholipase c-gamma1]]
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[[Category: sh2 domain-containing leukocyte phosphoprotein of 76 kd]]
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[[Category: sh3]]
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[[Category: slp-76]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:25:51 2007''
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Current revision

Phospholipase Cgamma1 SH3 in complex with a SLP-76 motif

PDB ID 1ywo

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