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3wa4
From Proteopedia
(Difference between revisions)
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| - | + | ==Grb2 SH2 domain/CD28-derived peptide complex== | |
| - | + | <StructureSection load='3wa4' size='340' side='right' caption='[[3wa4]], [[Resolution|resolution]] 1.35Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3wa4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WA4 FirstGlance]. <br> | |
| - | ==Function== | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene></td></tr> |
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRB2, ASH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wa4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wa4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wa4 RCSB], [http://www.ebi.ac.uk/pdbsum/3wa4 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
[[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. | [[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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| + | |||
| + | 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> | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | ==See Also== |
| - | + | *[[Growth factor receptor-bound protein|Growth factor receptor-bound protein]] | |
| - | [[Category: Higo, K | + | == References == |
| - | [[Category: Ito, N | + | <references/> |
| - | [[Category: Oda, M | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Higo, K]] | ||
| + | [[Category: Ito, N]] | ||
| + | [[Category: Oda, M]] | ||
[[Category: Grb2 sh2 domain]] | [[Category: Grb2 sh2 domain]] | ||
[[Category: Signaling protein]] | [[Category: Signaling protein]] | ||
Revision as of 22:37, 24 December 2014
Grb2 SH2 domain/CD28-derived peptide complex
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Categories: Human | Higo, K | Ito, N | Oda, M | Grb2 sh2 domain | Signaling protein
