3wa4

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{{STRUCTURE_3wa4| PDB=3wa4 | SCENE= }}
 
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===Grb2 SH2 domain/CD28-derived peptide complex===
 
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{{ABSTRACT_PUBMED_24098653}}
 
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==Function==
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==Grb2 SH2 domain/CD28-derived peptide complex==
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[[http://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> [[http://www.uniprot.org/uniprot/CD28_HUMAN CD28_HUMAN]] Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival.
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<StructureSection load='3wa4' size='340' side='right'caption='[[3wa4]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3wa4]] is a 2 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=3WA4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WA4 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]] 1.35&#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=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</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=3wa4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wa4 OCA], [https://pdbe.org/3wa4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wa4 RCSB], [https://www.ebi.ac.uk/pdbsum/3wa4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wa4 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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 A resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I beta-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I beta-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.
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==About this Structure==
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High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.,Higo K, Ikura T, Oda M, Morii H, Takahashi J, Abe R, Ito N PLoS One. 2013 Sep 30;8(9):e74482. doi: 10.1371/journal.pone.0074482. eCollection, 2013. PMID:24098653<ref>PMID:24098653</ref>
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[[3wa4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WA4 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:024098653</ref><references group="xtra"/><references/>
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</div>
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[[Category: Higo, K.]]
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<div class="pdbe-citations 3wa4" style="background-color:#fffaf0;"></div>
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[[Category: Ito, N.]]
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[[Category: Oda, M.]]
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==See Also==
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[[Category: Grb2 sh2 domain]]
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*[[Growth factor receptor-bound proteins 3D structures|Growth factor receptor-bound proteins 3D structures]]
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[[Category: Signaling protein]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Higo K]]
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[[Category: Ito N]]
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[[Category: Oda M]]

Current revision

Grb2 SH2 domain/CD28-derived peptide complex

PDB ID 3wa4

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