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{{STRUCTURE_1h3h|  PDB=1h3h  |  SCENE=  }}
===Structural Basis for Specific Recognition of an RxxK-containing SLP-76 peptide by the Gads C-terminal SH3 domain===
{{ABSTRACT_PUBMED_12620234}}


==Function==
==Structural Basis for Specific Recognition of an RxxK-containing SLP-76 peptide by the Gads C-terminal SH3 domain==
[[http://www.uniprot.org/uniprot/GRP2_MOUSE GRP2_MOUSE]] Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.<ref>PMID:9789079</ref> <ref>PMID:10777492</ref> <ref>PMID:10913189</ref> <ref>PMID:11432821</ref> <ref>PMID:11278453</ref> <ref>PMID:12239348</ref> <ref>PMID:15334074</ref> <ref>PMID:16357324</ref> <ref>PMID:17492052</ref> [[http://www.uniprot.org/uniprot/LCP2_HUMAN LCP2_HUMAN]] Involved in T-cell antigen receptor mediated signaling.  
<StructureSection load='1h3h' size='340' side='right'caption='[[1h3h]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1h3h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H3H FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h3h OCA], [https://pdbe.org/1h3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h3h RCSB], [https://www.ebi.ac.uk/pdbsum/1h3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h3h ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GRAP2_MOUSE GRAP2_MOUSE] Interacts with SLP-76 to regulate NF-AT activation. Binds to tyrosine-phosphorylated shc.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h3/1h3h_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1h3h ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The SH3 domain, which normally recognizes proline-rich sequences, has the potential to bind motifs with an RxxK consensus. To explore this novel specificity, we have determined the solution structure of the Gads T cell adaptor C-terminal SH3 domain in complex with an RSTK-containing peptide, representing its physiological binding site on the SLP-76 docking protein. The SLP-76 peptide engages four distinct binding pockets on the surface of the Gads SH3 domain and upon binding adopts a unique structure characterized by a right-handed 3(10) helix at the RSTK locus, in contrast to the left-handed polyproline type II helix formed by canonical proline-rich SH3 ligands. The structure, and supporting mutagenesis and peptide binding data, reveal a novel mode of ligand recognition by SH3 domains.


==About this Structure==
Structural basis for specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition.,Liu Q, Berry D, Nash P, Pawson T, McGlade CJ, Li SS Mol Cell. 2003 Feb;11(2):471-81. PMID:12620234<ref>PMID:12620234</ref>
[[1h3h]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H3H OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
<ref group="xtra">PMID:012620234</ref><references group="xtra"/><references/>
</div>
<div class="pdbe-citations 1h3h" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Berry, D.]]
[[Category: Berry D]]
[[Category: Li, S S.]]
[[Category: Li SS]]
[[Category: Liu, Q.]]
[[Category: Liu Q]]
[[Category: McGlade, C J.]]
[[Category: McGlade CJ]]
[[Category: Nash, P.]]
[[Category: Nash P]]
[[Category: Pawson, T.]]
[[Category: Pawson T]]
[[Category: Protein-binding]]
[[Category: Sh2 domain]]
[[Category: Sh3 domain]]
[[Category: T-cell signaling]]

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