2aug

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[[Image:2aug.gif|left|200px]]
 
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==Crystal structure of the Grb14 SH2 domain==
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The line below this paragraph, containing "STRUCTURE_2aug", creates the "Structure Box" on the page.
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<StructureSection load='2aug' size='340' side='right'caption='[[2aug]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2aug]] 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=2AUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AUG FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.3&#8491;</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=2aug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aug OCA], [https://pdbe.org/2aug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aug RCSB], [https://www.ebi.ac.uk/pdbsum/2aug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aug ProSAT]</span></td></tr>
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{{STRUCTURE_2aug| PDB=2aug | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GRB14_HUMAN GRB14_HUMAN] Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal.<ref>PMID:15210700</ref> <ref>PMID:19648926</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/au/2aug_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2aug 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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Grb14, a member of the Grb7 adaptor protein family, possesses a pleckstrin homology (PH) domain, a C-terminal Src homology-2 (SH2) domain, and an intervening stretch of approximately 45 residues known as the BPS region, which is unique to this adaptor family. Previous studies have demonstrated that Grb14 is a tissue-specific negative regulator of insulin receptor signaling and that inhibition is mediated by the BPS region. We have determined the crystal structure of the Grb14 BPS region in complex with the tyrosine kinase domain of the insulin receptor. The structure reveals that the N-terminal portion of the BPS region binds as a pseudosubstrate inhibitor in the substrate peptide binding groove of the kinase. Together with the crystal structure of the SH2 domain, we present a model for the interaction of Grb14 with the insulin receptor, which indicates how Grb14 functions as a selective protein inhibitor of insulin signaling.
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'''Crystal structure of the Grb14 SH2 domain'''
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Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14.,Depetris RS, Hu J, Gimpelevich I, Holt LJ, Daly RJ, Hubbard SR Mol Cell. 2005 Oct 28;20(2):325-33. PMID:16246733<ref>PMID:16246733</ref>
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==Overview==
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Grb14, a member of the Grb7 adaptor protein family, possesses a pleckstrin homology (PH) domain, a C-terminal Src homology-2 (SH2) domain, and an intervening stretch of approximately 45 residues known as the BPS region, which is unique to this adaptor family. Previous studies have demonstrated that Grb14 is a tissue-specific negative regulator of insulin receptor signaling and that inhibition is mediated by the BPS region. We have determined the crystal structure of the Grb14 BPS region in complex with the tyrosine kinase domain of the insulin receptor. The structure reveals that the N-terminal portion of the BPS region binds as a pseudosubstrate inhibitor in the substrate peptide binding groove of the kinase. Together with the crystal structure of the SH2 domain, we present a model for the interaction of Grb14 with the insulin receptor, which indicates how Grb14 functions as a selective protein inhibitor of insulin signaling.
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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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2AUG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AUG OCA].
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</div>
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<div class="pdbe-citations 2aug" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14., Depetris RS, Hu J, Gimpelevich I, Holt LJ, Daly RJ, Hubbard SR, Mol Cell. 2005 Oct 28;20(2):325-33. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16246733 16246733]
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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: Single protein]]
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[[Category: Large Structures]]
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[[Category: Daly, R J.]]
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[[Category: Daly RJ]]
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[[Category: Depetris, R S.]]
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[[Category: Depetris RS]]
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[[Category: Gimpelevich, I.]]
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[[Category: Gimpelevich I]]
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[[Category: Holt, L J.]]
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[[Category: Holt LJ]]
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[[Category: Hu, J.]]
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[[Category: Hu J]]
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[[Category: Hubbard, S R.]]
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[[Category: Hubbard SR]]
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[[Category: Phosphorylation]]
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[[Category: Sh2 domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:29:18 2008''
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Current revision

Crystal structure of the Grb14 SH2 domain

PDB ID 2aug

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