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==NMR STRUCTURE OF THE COMPLEX BETWEEN THE C32S-Y7V MUTANT OF THE NSH3 DOMAIN OF GRB2 WITH A PEPTIDE FROM SOS, 10 STRUCTURES==
==NMR STRUCTURE OF THE COMPLEX BETWEEN THE C32S-Y7V MUTANT OF THE NSH3 DOMAIN OF GRB2 WITH A PEPTIDE FROM SOS, 10 STRUCTURES==
<StructureSection load='1aze' size='340' side='right'caption='[[1aze]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
<StructureSection load='1aze' size='340' side='right'caption='[[1aze]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1aze]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome] and [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AZE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AZE FirstGlance]. <br>
<table><tr><td colspan='2'>[[1aze]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AZE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AZE FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRB2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
</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=1aze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1aze OCA], [https://pdbe.org/1aze PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1aze RCSB], [https://www.ebi.ac.uk/pdbsum/1aze PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1aze ProSAT]</span></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=1aze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1aze OCA], [https://pdbe.org/1aze PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1aze RCSB], [https://www.ebi.ac.uk/pdbsum/1aze PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1aze ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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> [[https://www.uniprot.org/uniprot/SOS_DROME SOS_DROME]] Promotes the exchange of Ras-bound GDP by GTP. Functions in signaling pathways initiated by the sevenless and epidermal growth factor receptor tyrosine kinases; implies a role for the ras pathway in neuronal development.<ref>PMID:1736363</ref> <ref>PMID:1934068</ref> 
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=1aze ConSurf].
</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=1aze ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Quantitative analysis of Grb2/dynamin interaction through plasmon resonance analysis (BIAcore) using Grb2 mutants showed that the high affinity measured between Grb2 and dynamin is essentially mediated by the N-SH3 domain of Grb2. In order to study the interactions between Grb2 and either dynamin or Sos in more detail, Grb2 N-SH3 domains containing different mutations have been analysed. Two mutations were located on the hydrophobic platform binding proline-rich peptides (Y7V and P49L) and one (E40T) located in a region that we had previously shown to be essential for Grb2/dynamin interactions. Through NMR analysis, we have clearly demonstrated that the structure of the P49L mutant is not folded, while the other E40T and Y7V mutants adopt folded structures that are quite similar to that described for the reference domain. Nevertheless, these point mutations were shown to alter the overall stability of these domains by inducing an equilibrium between a folded and an unfolded form. The complex formed between the peptide VPPPVPPRRR, derived from Sos, and the E40T mutant was shown to have the same 3D structure as that described for the wild-type SH3 domain. However, the VPPPVPPRRR peptide adopts a slightly different orientation when it is complexed with the Y7V mutant. Finally, the affinity of the proline-rich peptide GPPPQVPSRPNR, derived from dynamin, for the Grb2 N-SH3 domain was too low to be analyzed by NMR. Thus, the interaction between either Sos or dynamin and the SH3 mutants were tested on a cellular homogenate by means of a far-Western blot analysis. In these conditions, the P49L mutant was shown to be devoid of affinity for Sos as well as for dynamin. The Y7V SH3 mutant displayed a decrease of affinity for both Sos and dynamin, while the E40T mutant exhibited a decrease of affinity only for dynamin. These results support the existence of two binding sites between dynamin and the Grb2 N-SH3 domain.
Molecular and cellular analysis of Grb2 SH3 domain mutants: interaction with Sos and dynamin.,Vidal M, Goudreau N, Cornille F, Cussac D, Gincel E, Garbay C J Mol Biol. 1999 Jul 16;290(3):717-30. PMID:10395825<ref>PMID:10395825</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1aze" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Drome]]
[[Category: Drosophila melanogaster]]
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Cornille, F]]
[[Category: Cornille F]]
[[Category: Duchesne, M]]
[[Category: Duchesne M]]
[[Category: Garbay, C]]
[[Category: Garbay C]]
[[Category: Gincel, E]]
[[Category: Gincel E]]
[[Category: Goudreau, N]]
[[Category: Goudreau N]]
[[Category: Parker, F]]
[[Category: Parker F]]
[[Category: Roques, B P]]
[[Category: Roques BP]]
[[Category: Tocque, B]]
[[Category: Tocque B]]
[[Category: Vidal, M]]
[[Category: Vidal M]]
[[Category: Guanine-nucleotide releasing factor]]
[[Category: Sh3 domain]]
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