2auh: Difference between revisions

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[[Image:2auh.png|left|200px]]


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==Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase==
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<StructureSection load='2auh' size='340' side='right'caption='[[2auh]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2auh]] 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=2AUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AUH 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]] 3.2&#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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
{{STRUCTURE_2auh|  PDB=2auh  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2auh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2auh OCA], [https://pdbe.org/2auh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2auh RCSB], [https://www.ebi.ac.uk/pdbsum/2auh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2auh ProSAT]</span></td></tr>
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== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
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    <text>to colour the structure by Evolutionary Conservation</text>
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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=2auh ConSurf].
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== Publication Abstract from PubMed ==
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.


===Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase===
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>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_16246733}}, adds the Publication Abstract to the page
*[[Growth factor receptor-bound proteins 3D structures|Growth factor receptor-bound proteins 3D structures]]
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*[[Insulin receptor 3D structures|Insulin receptor 3D structures]]
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== References ==
{{ABSTRACT_PUBMED_16246733}}
<references/>
 
__TOC__
==Disease==
</StructureSection>
Known disease associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Leprechaunism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Rabson-Mendenhall syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]]
 
==About this Structure==
2AUH is a 2 chains structure of sequences 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=2AUH OCA].
 
==Reference==
<ref group="xtra">PMID:16246733</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Transferase]]
[[Category: Large Structures]]
[[Category: Daly, R J.]]
[[Category: Daly RJ]]
[[Category: Depetris, R S.]]
[[Category: Depetris RS]]
[[Category: Gimpelevich, I.]]
[[Category: Gimpelevich I]]
[[Category: Holt, L J.]]
[[Category: Holt LJ]]
[[Category: Hu, J.]]
[[Category: Hu J]]
[[Category: Hubbard, S R.]]
[[Category: Hubbard SR]]
[[Category: Bps region]]
[[Category: Transferase/signaling protein complex]]
[[Category: Tyrosine kinase]]
 
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