2o95

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[[Image:2o95.gif|left|200px]]<br /><applet load="2o95" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2o95, resolution 1.950&Aring;" />
 
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'''Crystal Structure of the Metal-Free Dimeric Human Mov34 MPN domain (residues 1-186)'''<br />
 
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==Overview==
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==Crystal Structure of the Metal-Free Dimeric Human Mov34 MPN domain (residues 1-186)==
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The 26S proteasome is a large protein complex involved in protein, degradation. We have shown previously that the PSMD7/Mov34 subunit of the, human proteasome contains a proteolytically resistant MPN domain. MPN, domain family members comprise subunits of the proteasome, COP9-signalosome and translation initiation factor 3 complexes. Here, the, crystal structure of two C-terminally truncated proteins, MPN 1-186 and, MPN 1-177, were solved to 1.96 and 3.0 A resolution, respectively. MPN, 1-186 is formed by nine beta-strands surrounded by three alpha-helices, plus a fourth alpha-helix at the C terminus. This final alpha-helix, emerges from the domain core and folds along with a symmetrically related, subunit, typical of a domain swap. The crystallographic dimer is, consistent with size-exclusion chromatography and DLS analysis showing, that MPN 1-186 is a dimer in solution. MPN 1-186 shows an overall, architecture highly similar to the previously reported crystal structure, of the Archaeal MPN domain AfJAMM of Archaeoglobus fulgidus. However, previous structural and biophysical analyses have shown that neither MPN, 1-186 nor full-length human Mov34 bind metal, in opposition to the, zinc-binding AfJAMM structures. The zinc ligand residues observed in, AfJAMM are conserved in the yeast Rpn11 proteasome and Csn5, COP-signalosome subunits, which is consistent with the isopeptidase, activity described for these proteins. The results presented here show, that, although the MPN domain of Mov34 shows a typical metalloprotease, fold, it is unable to coordinate a metal ion. This finding and amino acid, sequence comparisons can explain why the MPN-containing proteins, Mov34/PSMD7, RPN8, Csn6, Prp8p and the translation initiation factor 3, subunits f and h do not show catalytic isopeptidase activity, allowing us, to propose the hypothesis that in these proteins the MPN domain has a, primarily structural function.
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<StructureSection load='2o95' size='340' side='right'caption='[[2o95]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2o95]] 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=2O95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O95 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]] 1.95&#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=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=ETE:2-{2-[2-2-(METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>ETE</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2o95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o95 OCA], [https://pdbe.org/2o95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o95 RCSB], [https://www.ebi.ac.uk/pdbsum/2o95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o95 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PSMD7_HUMAN PSMD7_HUMAN] Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.
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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/o9/2o95_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=2o95 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 26S proteasome is a large protein complex involved in protein degradation. We have shown previously that the PSMD7/Mov34 subunit of the human proteasome contains a proteolytically resistant MPN domain. MPN domain family members comprise subunits of the proteasome, COP9-signalosome and translation initiation factor 3 complexes. Here, the crystal structure of two C-terminally truncated proteins, MPN 1-186 and MPN 1-177, were solved to 1.96 and 3.0 A resolution, respectively. MPN 1-186 is formed by nine beta-strands surrounded by three alpha-helices plus a fourth alpha-helix at the C terminus. This final alpha-helix emerges from the domain core and folds along with a symmetrically related subunit, typical of a domain swap. The crystallographic dimer is consistent with size-exclusion chromatography and DLS analysis showing that MPN 1-186 is a dimer in solution. MPN 1-186 shows an overall architecture highly similar to the previously reported crystal structure of the Archaeal MPN domain AfJAMM of Archaeoglobus fulgidus. However, previous structural and biophysical analyses have shown that neither MPN 1-186 nor full-length human Mov34 bind metal, in opposition to the zinc-binding AfJAMM structures. The zinc ligand residues observed in AfJAMM are conserved in the yeast Rpn11 proteasome and Csn5 COP-signalosome subunits, which is consistent with the isopeptidase activity described for these proteins. The results presented here show that, although the MPN domain of Mov34 shows a typical metalloprotease fold, it is unable to coordinate a metal ion. This finding and amino acid sequence comparisons can explain why the MPN-containing proteins Mov34/PSMD7, RPN8, Csn6, Prp8p and the translation initiation factor 3 subunits f and h do not show catalytic isopeptidase activity, allowing us to propose the hypothesis that in these proteins the MPN domain has a primarily structural function.
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==About this Structure==
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The crystal structure of the human Mov34 MPN domain reveals a metal-free dimer.,Sanches M, Alves BS, Zanchin NI, Guimaraes BG J Mol Biol. 2007 Jul 27;370(5):846-55. Epub 2007 May 10. PMID:17559875<ref>PMID:17559875</ref>
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2O95 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 <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=12P:'>12P</scene>, <scene name='pdbligand=ETE:'>ETE</scene>, <scene name='pdbligand=PG4:'>PG4</scene> and <scene name='pdbligand=PGE:'>PGE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O95 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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The Crystal Structure of the Human Mov34 MPN Domain Reveals a Metal-free Dimer., Sanches M, Alves BS, Zanchin NI, Guimaraes BG, J Mol Biol. 2007 Jul 27;370(5):846-55. Epub 2007 May 10. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17559875 17559875]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2o95" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Alves, B.S.C.]]
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[[Category: Guimaraes, B.G.]]
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[[Category: Sanches, M.]]
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[[Category: Zanchin, N.I.T.]]
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[[Category: 12P]]
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[[Category: ETE]]
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[[Category: PG4]]
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[[Category: PGE]]
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[[Category: SO4]]
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[[Category: 26s proteasome]]
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[[Category: jab1/mpn]]
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[[Category: metal-free dimer]]
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[[Category: mov34]]
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[[Category: psmd7]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:31:41 2008''
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==See Also==
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*[[Proteasome 3D structures|Proteasome 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Alves BSC]]
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[[Category: Guimaraes BG]]
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[[Category: Sanches M]]
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[[Category: Zanchin NIT]]

Current revision

Crystal Structure of the Metal-Free Dimeric Human Mov34 MPN domain (residues 1-186)

PDB ID 2o95

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