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New page: left|200px<br /> <applet load="1mfl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mfl, resolution 1.88Å" /> '''The Structure of ER...
 
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[[Image:1mfl.gif|left|200px]]<br />
<applet load="1mfl" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1mfl, resolution 1.88&Aring;" />
'''The Structure of ERBIN PDZ domain bound to the Carboxy-terminal tail of the ErbB2 Receptor'''<br />


==Overview==
==The Structure of ERBIN PDZ domain bound to the Carboxy-terminal tail of the ErbB2 Receptor==
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.
<StructureSection load='1mfl' size='340' side='right'caption='[[1mfl]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.88&#8491;</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'>[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>
== Function ==
[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 ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <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/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1mfl ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==About this Structure==
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<ref>PMID:12444095</ref>
1MFL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MFL OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12444095 12444095]
</div>
<div class="pdbe-citations 1mfl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Birrane, G.]]
[[Category: Birrane G]]
[[Category: Chung, J.]]
[[Category: Chung J]]
[[Category: Ladias, J.A.]]
[[Category: Ladias JA]]
[[Category: erb-b2]]
[[Category: erbin]]
[[Category: pdz domain]]
[[Category: phosphorylation]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:10:41 2007''

Latest revision as of 00:14, 21 November 2024

The Structure of ERBIN PDZ domain bound to the Carboxy-terminal tail of the ErbB2 Receptor

1mfl, resolution 1.88Å

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