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3wa4

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Revision as of 03:43, 5 August 2016

Grb2 SH2 domain/CD28-derived peptide complex

Structural highlights

3wa4 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Gene:	GRB2, ASH (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [CD28_HUMAN] Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival.

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Higo K, Ikura T, Oda M, Morii H, Takahashi J, Abe R, Ito N. High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28. PLoS One. 2013 Sep 30;8(9):e74482. doi: 10.1371/journal.pone.0074482. eCollection, 2013. PMID:24098653 doi:http://dx.doi.org/10.1371/journal.pone.0074482

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3wa4"

@@ Line 1: / Line 1: @@
 ==Grb2 SH2 domain/CD28-derived peptide complex==
 <StructureSection load='3wa4' size='340' side='right' caption='[[3wa4]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <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>
+<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://pdbe.org/3wa4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wa4 RCSB], [http://www.ebi.ac.uk/pdbsum/3wa4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wa4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3wa4" style="background-color:#fffaf0;"></div>
 ==See Also==

3wa4

From Proteopedia

Revision as of 03:43, 5 August 2016

Grb2 SH2 domain/CD28-derived peptide complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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