1zvd

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(New page: 200px<br /> <applet load="1zvd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zvd, resolution 2.10&Aring;" /> '''Regulation of Smurf...)
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[[Image:1zvd.gif|left|200px]]<br />
 
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<applet load="1zvd" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1zvd, resolution 2.10&Aring;" />
 
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'''Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain'''<br />
 
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==Overview==
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==Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain==
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The conjugation of ubiquitin to proteins involves a cascade of activating, (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that, commonly signal protein destruction. In TGFbeta signaling the inhibitory, protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to, the TGFbeta receptor complex to facilitate receptor degradation. Here, we, demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf, activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A, resolution X-ray crystal structure of the Smurf2 HECT domain reveals that, it has a suboptimal E2 binding pocket that could be optimized by, mutagenesis to generate a HECT domain that functions independently of, Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition, by an E3 HECT enzyme is not constitutively competent and provides a point, of control for regulating the ubiquitin ligase activity through the action, of auxiliary proteins.
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<StructureSection load='1zvd' size='340' side='right'caption='[[1zvd]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1zvd]] is a 1 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=1ZVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZVD 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]] 2.1&#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=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=1zvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zvd OCA], [https://pdbe.org/1zvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zvd RCSB], [https://www.ebi.ac.uk/pdbsum/1zvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zvd ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SMUF2_HUMAN SMUF2_HUMAN] E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as SNON, for ubiquitin-mediated degradation. Enhances the inhibitory activity of SMAD7 and reduces the transcriptional activity of SMAD2. Coexpression of SMURF2 with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein and a smaller decrease of SMAD2 level.<ref>PMID:11389444</ref> <ref>PMID:12717440</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/zv/1zvd_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1zvd 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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The conjugation of ubiquitin to proteins involves a cascade of activating (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that commonly signal protein destruction. In TGFbeta signaling the inhibitory protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to facilitate receptor degradation. Here, we demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A resolution X-ray crystal structure of the Smurf2 HECT domain reveals that it has a suboptimal E2 binding pocket that could be optimized by mutagenesis to generate a HECT domain that functions independently of Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition by an E3 HECT enzyme is not constitutively competent and provides a point of control for regulating the ubiquitin ligase activity through the action of auxiliary proteins.
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==About this Structure==
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Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain.,Ogunjimi AA, Briant DJ, Pece-Barbara N, Le Roy C, Di Guglielmo GM, Kavsak P, Rasmussen RK, Seet BT, Sicheri F, Wrana JL Mol Cell. 2005 Aug 5;19(3):297-308. PMID:16061177<ref>PMID:16061177</ref>
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1ZVD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NA and PO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZVD OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain., Ogunjimi AA, Briant DJ, Pece-Barbara N, Le Roy C, Di Guglielmo GM, Kavsak P, Rasmussen RK, Seet BT, Sicheri F, Wrana JL, Mol Cell. 2005 Aug 5;19(3):297-308. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16061177 16061177]
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</div>
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<div class="pdbe-citations 1zvd" style="background-color:#fffaf0;"></div>
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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: Briant, D.J.]]
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[[Category: Briant DJ]]
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[[Category: Guglielmo, G.M.Di.]]
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[[Category: Di Guglielmo GM]]
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[[Category: Kavsak, P.]]
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[[Category: Kavsak P]]
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[[Category: Ogunjimi, A.A.]]
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[[Category: Le Roy C]]
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[[Category: Pece-Barbara, N.]]
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[[Category: Ogunjimi AA]]
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[[Category: Rasmussen, R.K.]]
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[[Category: Pece-Barbara N]]
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[[Category: Roy, C.Le.]]
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[[Category: Rasmussen RK]]
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[[Category: Seet, B.T.]]
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[[Category: Seet BT]]
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[[Category: Sicheri, F.]]
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[[Category: Sicheri F]]
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[[Category: Wrana, J.L.]]
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[[Category: Wrana JL]]
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[[Category: NA]]
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[[Category: PO4]]
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[[Category: tgfbeta]]
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[[Category: ubiquitin ligasecatalytic mechanism]]
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[[Category: x-ray crystal structure]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:41:50 2007''
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Current revision

Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain

PDB ID 1zvd

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