1fyr

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(New page: 200px<br /> <applet load="1fyr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fyr, resolution 2.40&Aring;" /> '''DIMER FORMATION THR...)
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[[Image:1fyr.gif|left|200px]]<br />
 
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<applet load="1fyr" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1fyr, resolution 2.40&Aring;" />
 
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'''DIMER FORMATION THROUGH DOMAIN SWAPPING IN THE CRYSTAL STRUCTURE OF THE GRB2-SH2 AC-PYVNV COMPLEX'''<br />
 
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==Overview==
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==DIMER FORMATION THROUGH DOMAIN SWAPPING IN THE CRYSTAL STRUCTURE OF THE GRB2-SH2 AC-PYVNV COMPLEX==
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Src homology 2 (SH2) domains are key modules in intracellular signal, transduction. They link activated cell surface receptors to downstream, targets by binding to phosphotyrosine-containing sequence motifs. The, crystal structure of a Grb2-SH2 domain-phosphopeptide complex was, determined at 2.4 A resolution. The asymmetric unit contains four, polypeptide chains. There is an unexpected domain swap so that individual, chains do not adopt a closed SH2 fold. Instead, reorganization of the EF, loop leads to an open, nonglobular fold, which associates with an, equivalent partner to generate an intertwined dimer. As in previously, reported crystal structures of canonical Grb2-SH2 domain-peptide, complexes, each of the four hybrid SH2 domains in the two domain-swapped, dimers binds the phosphopeptide in a type I beta-turn conformation. This, report is the first to describe domain swapping for an SH2 domain. While, in vivo evidence of dimerization of Grb2 exists, our SH2 dimer is, metastable and a physiological role of this new form of dimer formation, remains to be demonstrated.
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<StructureSection load='1fyr' size='340' side='right'caption='[[1fyr]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1fyr]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FYR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FYR 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]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=1fyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fyr OCA], [https://pdbe.org/1fyr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fyr RCSB], [https://www.ebi.ac.uk/pdbsum/1fyr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fyr 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/fy/1fyr_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1fyr ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Src homology 2 (SH2) domains are key modules in intracellular signal transduction. They link activated cell surface receptors to downstream targets by binding to phosphotyrosine-containing sequence motifs. The crystal structure of a Grb2-SH2 domain-phosphopeptide complex was determined at 2.4 A resolution. The asymmetric unit contains four polypeptide chains. There is an unexpected domain swap so that individual chains do not adopt a closed SH2 fold. Instead, reorganization of the EF loop leads to an open, nonglobular fold, which associates with an equivalent partner to generate an intertwined dimer. As in previously reported crystal structures of canonical Grb2-SH2 domain-peptide complexes, each of the four hybrid SH2 domains in the two domain-swapped dimers binds the phosphopeptide in a type I beta-turn conformation. This report is the first to describe domain swapping for an SH2 domain. While in vivo evidence of dimerization of Grb2 exists, our SH2 dimer is metastable and a physiological role of this new form of dimer formation remains to be demonstrated.
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==Disease==
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Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex.,Schiering N, Casale E, Caccia P, Giordano P, Battistini C Biochemistry. 2000 Nov 7;39(44):13376-82. PMID:11063574<ref>PMID:11063574</ref>
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Known diseases associated with this structure: Autism, suseptibility to, 9 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]], 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]], Hepatocellular carcinoma, childhood type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]], Renal cell carcinoma, papillary, familial and sporadic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1FYR is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ACE as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FYR OCA].
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</div>
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<div class="pdbe-citations 1fyr" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex., Schiering N, Casale E, Caccia P, Giordano P, Battistini C, Biochemistry. 2000 Nov 7;39(44):13376-82. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11063574 11063574]
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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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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Battistini, C.]]
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[[Category: Battistini C]]
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[[Category: Caccia, P.]]
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[[Category: Caccia P]]
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[[Category: Casale, E.]]
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[[Category: Casale E]]
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[[Category: Giordano, P.]]
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[[Category: Giordano P]]
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[[Category: Schiering, N.]]
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[[Category: Schiering N]]
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[[Category: ACE]]
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[[Category: dimerization]]
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[[Category: domain swapping]]
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[[Category: grb2]]
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[[Category: met]]
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[[Category: phosphopeptide]]
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[[Category: sh2 domain]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:58:23 2007''
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Current revision

DIMER FORMATION THROUGH DOMAIN SWAPPING IN THE CRYSTAL STRUCTURE OF THE GRB2-SH2 AC-PYVNV COMPLEX

PDB ID 1fyr

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