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| | ==The Structure of ERBIN PDZ domain bound to the Carboxy-terminal tail of the ErbB2 Receptor== | | ==The Structure of ERBIN PDZ domain bound to the Carboxy-terminal tail of the ErbB2 Receptor== |
| - | <StructureSection load='1mfl' size='340' side='right' caption='[[1mfl]], [[Resolution|resolution]] 1.88Å' scene=''> | + | <StructureSection load='1mfl' size='340' side='right'caption='[[1mfl]], [[Resolution|resolution]] 1.88Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1mfl]] 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=1MFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1MFL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1mfl]] 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=1MFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MFL FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.88Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mfg|1mfg]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=1mfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mfl OCA], [http://pdbe.org/1mfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1mfl RCSB], [http://www.ebi.ac.uk/pdbsum/1mfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1mfl ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mfl OCA], [https://pdbe.org/1mfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mfl RCSB], [https://www.ebi.ac.uk/pdbsum/1mfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mfl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LAP2_HUMAN LAP2_HUMAN]] Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state.<ref>PMID:10878805</ref> | + | [https://www.uniprot.org/uniprot/ERBIN_HUMAN ERBIN_HUMAN] Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state (PubMed:16203728). Inhibits NOD2-dependent NF-kappa-B signaling and proinflammatory cytokine secretion (PubMed:16203728).<ref>PMID:10878805</ref> <ref>PMID:16203728</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mf/1mfl_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mf/1mfl_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Birrane, G]] | + | [[Category: Large Structures]] |
| - | [[Category: Chung, J]] | + | [[Category: Birrane G]] |
| - | [[Category: Ladias, J A]] | + | [[Category: Chung J]] |
| - | [[Category: Erb-b2]] | + | [[Category: Ladias JA]] |
| - | [[Category: Erbin]]
| + | |
| - | [[Category: Pdz domain]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
ERBIN_HUMAN Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state (PubMed:16203728). Inhibits NOD2-dependent NF-kappa-B signaling and proinflammatory cytokine secretion (PubMed:16203728).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Erbin contains a class I PDZ domain that binds to the C-terminal region of the receptor tyrosine kinase ErbB2, a class II ligand. The crystal structure of the human Erbin PDZ bound to the peptide EYLGLDVPV corresponding to the C-terminal residues 1247-1255 of human ErbB2 has been determined at 1.25-A resolution. The Erbin PDZ deviates from the canonical PDZ fold in that it contains a single alpha-helix. The isopropyl group of valine at position -2 of the ErbB2 peptide interacts with the Erbin Val(1351) and displaces the peptide backbone away from the alpha-helix, elucidating the molecular basis of class II ligand recognition by a class I PDZ domain. Strikingly, the phenolic ring of tyrosine -7 enters into a pocket formed by the extended beta 2-beta 3 loop of the Erbin PDZ. Phosphorylation of tyrosine -7 abolishes this interaction but does not affect the binding of the four C-terminal peptidic residues to PDZ, as revealed by the crystal structure of the Erbin PDZ complexed with a phosphotyrosine-containing ErbB2 peptide. Since phosphorylation of tyrosine -7 plays a critical role in ErbB2 function, the selective binding and sequestration of this residue in its unphosphorylated state by the Erbin PDZ provides a novel mechanism for regulation of the ErbB2-mediated signaling and oncogenicity.
Novel mode of ligand recognition by the Erbin PDZ domain.,Birrane G, Chung J, Ladias JA J Biol Chem. 2003 Jan 17;278(3):1399-402. Epub 2002 Nov 19. PMID:12444095[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, Fournier E, Adelaide J, Margolis B, Birnbaum D. ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. Nat Cell Biol. 2000 Jul;2(7):407-14. PMID:10878805 doi:10.1038/35017038
- ↑ McDonald C, Chen FF, Ollendorff V, Ogura Y, Marchetto S, Lecine P, Borg JP, Nunez G. A role for Erbin in the regulation of Nod2-dependent NF-kappaB signaling. J Biol Chem. 2005 Dec 2;280(48):40301-9. doi: 10.1074/jbc.M508538200. Epub 2005, Oct 3. PMID:16203728 doi:http://dx.doi.org/10.1074/jbc.M508538200
- ↑ Birrane G, Chung J, Ladias JA. Novel mode of ligand recognition by the Erbin PDZ domain. J Biol Chem. 2003 Jan 17;278(3):1399-402. Epub 2002 Nov 19. PMID:12444095 doi:http://dx.doi.org/10.1074/jbc.C200571200
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