1gfc

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[[Image:1gfc.gif|left|200px]]<br /><applet load="1gfc" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1gfc" />
 
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'''SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE C-TERMINAL SH3 DOMAIN OF GRB2'''<br />
 
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==Overview==
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==SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE C-TERMINAL SH3 DOMAIN OF GRB2==
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BACKGROUND: Growth factor receptor-bound protein 2 (GRB2) is an adaptor protein with three Src homology (SH) domains in the order SH3-SH2-SH3. Both SH3 domains of GRB2 are necessary for interaction with the protein Son of sevenless (Sos), which acts as a Ras activator. Thus, GRB2 mediates signal transduction from growth factor receptors to Ras and is thought to be a key molecule in signal transduction. RESULTS: The three-dimensional structure of the carboxy-terminal SH3 domain of GRB2 (GRB2 C-SH3) was determined by NMR spectroscopy. The SH3 structure consists of six beta-strands arranged in two beta-sheets that are packed together perpendicularly with two additional beta-strands forming the third beta-sheet. GRB2 C-SH3 is very similar to SH3 domains from other proteins. The binding site of the ligand peptide (VPP-PVPPRRR) derived from the Sos protein was mapped on the GRB2 C-SH3 domain indirectly using 1H and 15N chemical shift changes, and directly using several intermolecular nuclear Overhauser effects. CONCLUSIONS: Despite the structural similarity among the known SH3 domains, the sequence alignment and the secondary structure assignments differ. We therefore propose a standard description of the SH3 structures to facilitate comparison of individual SH3 domains, based on their three-dimensional structures. The binding site of the ligand peptide on GRB2 C-SH3 is in good agreement with those found in other SH3 domains.
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<StructureSection load='1gfc' size='340' side='right'caption='[[1gfc]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1gfc]] is a 1 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=1GFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GFC 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">Solution NMR</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=1gfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gfc OCA], [https://pdbe.org/1gfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gfc RCSB], [https://www.ebi.ac.uk/pdbsum/1gfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gfc ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GRB2_HUMAN GRB2_HUMAN] Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.<ref>PMID:1322798</ref> <ref>PMID:8178156</ref> <ref>PMID:19815557</ref> Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.<ref>PMID:1322798</ref> <ref>PMID:8178156</ref> <ref>PMID:19815557</ref>
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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/gf/1gfc_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=1gfc ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Central hypoventilation syndrome, congenital OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=100790 100790]], Haddad syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=100790 100790]]
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*[[Growth factor receptor-bound proteins 3D structures|Growth factor receptor-bound proteins 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1GFC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GFC OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2., Kohda D, Terasawa H, Ichikawa S, Ogura K, Hatanaka H, Mandiyan V, Ullrich A, Schlessinger J, Inagaki F, Structure. 1994 Nov 15;2(11):1029-40. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7881903 7881903]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Hatanaka, H.]]
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[[Category: Hatanaka H]]
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[[Category: Inagaki, F.]]
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[[Category: Inagaki F]]
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[[Category: Kohda, D.]]
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[[Category: Kohda D]]
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[[Category: Terasawa, H.]]
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[[Category: Terasawa H]]
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[[Category: adaptor protein containing sh2 and sh3]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:49:25 2008''
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Current revision

SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE C-TERMINAL SH3 DOMAIN OF GRB2

PDB ID 1gfc

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