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- | [[Image:1gfc.gif|left|200px]] | |
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- | {{Structure
| + | ==SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE C-TERMINAL SH3 DOMAIN OF GRB2== |
- | |PDB= 1gfc |SIZE=350|CAPTION= <scene name='initialview01'>1gfc</scene>
| + | <StructureSection load='1gfc' size='340' side='right'caption='[[1gfc]]' scene=''> |
- | |SITE=
| + | == Structural highlights == |
- | |LIGAND=
| + | <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> |
- | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
- | |GENE= GRB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <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> |
- | |DOMAIN=
| + | </table> |
- | |RELATEDENTRY=[[1gfd|1GFD]]
| + | == Function == |
- | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gfc OCA], [http://www.ebi.ac.uk/pdbsum/1gfc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gfc RCSB]</span>
| + | [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> |
- | }}
| + | == 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/gf/1gfc_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=1gfc ConSurf]. |
| + | <div style="clear:both"></div> |
| | | |
- | '''SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE C-TERMINAL SH3 DOMAIN OF GRB2'''
| + | ==See Also== |
- | | + | *[[Growth factor receptor-bound proteins 3D structures|Growth factor receptor-bound proteins 3D structures]] |
- | | + | == References == |
- | ==Overview== | + | <references/> |
- | 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.
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure== | + | |
- | 1GFC is a [[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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- | | + | |
- | ==Reference==
| + | |
- | 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://www.ncbi.nlm.nih.gov/pubmed/7881903 7881903]
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| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
- | [[Category: Single protein]] | + | [[Category: Large Structures]] |
- | [[Category: Hatanaka, H.]] | + | [[Category: Hatanaka H]] |
- | [[Category: Inagaki, F.]] | + | [[Category: Inagaki F]] |
- | [[Category: Kohda, D.]] | + | [[Category: Kohda D]] |
- | [[Category: Terasawa, H.]] | + | [[Category: Terasawa H]] |
- | [[Category: adaptor protein containing sh2 and sh3]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:42:47 2008''
| + | |
| Structural highlights
Function
GRB2_HUMAN Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.[1] [2] [3] 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.[4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992 Aug 7;70(3):431-42. PMID:1322798
- ↑ Fath I, Schweighoffer F, Rey I, Multon MC, Boiziau J, Duchesne M, Tocque B. Cloning of a Grb2 isoform with apoptotic properties. Science. 1994 May 13;264(5161):971-4. PMID:8178156
- ↑ Pao-Chun L, Chan PM, Chan W, Manser E. Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. J Biol Chem. 2009 Dec 11;284(50):34954-63. doi: 10.1074/jbc.M109.072660. Epub, 2009 Oct 8. PMID:19815557 doi:10.1074/jbc.M109.072660
- ↑ Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992 Aug 7;70(3):431-42. PMID:1322798
- ↑ Fath I, Schweighoffer F, Rey I, Multon MC, Boiziau J, Duchesne M, Tocque B. Cloning of a Grb2 isoform with apoptotic properties. Science. 1994 May 13;264(5161):971-4. PMID:8178156
- ↑ Pao-Chun L, Chan PM, Chan W, Manser E. Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. J Biol Chem. 2009 Dec 11;284(50):34954-63. doi: 10.1074/jbc.M109.072660. Epub, 2009 Oct 8. PMID:19815557 doi:10.1074/jbc.M109.072660
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