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New page: left|200px<br /><applet load="2gmi" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gmi, resolution 2.500Å" /> '''Mms2/Ubc13~Ubiquiti...
 
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[[Image:2gmi.jpg|left|200px]]<br /><applet load="2gmi" size="450" color="white" frame="true" align="right" spinBox="true"
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'''Mms2/Ubc13~Ubiquitin'''<br />


==Overview==
==Mms2/Ubc13~Ubiquitin==
Lys63-linked polyubiquitin chains participate in nonproteolytic signaling, pathways, including regulation of DNA damage tolerance and NF-kappaB, activation. E2 enzymes bound to ubiquitin E2 variants (UEV) are vital in, these pathways, synthesizing Lys63-linked polyubiquitin chains, but how, these complexes achieve specificity for a particular lysine linkage has, been unclear. We have determined the crystal structure of an, Mms2-Ubc13-ubiquitin (UEV-E2-Ub) covalent intermediate with donor, ubiquitin linked to the active site residue of Ubc13. In the structure, the unexpected binding of a donor ubiquitin of one Mms2-Ubc13-Ub complex, to the acceptor-binding site of Mms2-Ubc13 in an adjacent complex allows, us to visualize at atomic resolution the molecular determinants of, acceptor-ubiquitin binding. The structure reveals the key role of Mms2 in, allowing selective insertion of Lys63 into the Ubc13 active site and, suggests a molecular model for polyubiquitin chain elongation.
<StructureSection load='2gmi' size='340' side='right'caption='[[2gmi]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2gmi]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GMI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GMI 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]] 2.5&#8491;</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=2gmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gmi OCA], [https://pdbe.org/2gmi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gmi RCSB], [https://www.ebi.ac.uk/pdbsum/2gmi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gmi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UBC13_YEAST UBC13_YEAST] Has a role in the DNA error-free postreplication repair (PRR) pathway. The UBC13/MMS2 heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'.
== 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/gm/2gmi_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=2gmi ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lys63-linked polyubiquitin chains participate in nonproteolytic signaling pathways, including regulation of DNA damage tolerance and NF-kappaB activation. E2 enzymes bound to ubiquitin E2 variants (UEV) are vital in these pathways, synthesizing Lys63-linked polyubiquitin chains, but how these complexes achieve specificity for a particular lysine linkage has been unclear. We have determined the crystal structure of an Mms2-Ubc13-ubiquitin (UEV-E2-Ub) covalent intermediate with donor ubiquitin linked to the active site residue of Ubc13. In the structure, the unexpected binding of a donor ubiquitin of one Mms2-Ubc13-Ub complex to the acceptor-binding site of Mms2-Ubc13 in an adjacent complex allows us to visualize at atomic resolution the molecular determinants of acceptor-ubiquitin binding. The structure reveals the key role of Mms2 in allowing selective insertion of Lys63 into the Ubc13 active site and suggests a molecular model for polyubiquitin chain elongation.


==About this Structure==
Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation.,Eddins MJ, Carlile CM, Gomez KM, Pickart CM, Wolberger C Nat Struct Mol Biol. 2006 Oct;13(10):915-20. Epub 2006 Sep 17. PMID:16980971<ref>PMID:16980971</ref>
2GMI is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Active as [http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2GMI OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation., Eddins MJ, Carlile CM, Gomez KM, Pickart CM, Wolberger C, Nat Struct Mol Biol. 2006 Oct;13(10):915-20. Epub 2006 Sep 17. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16980971 16980971]
</div>
<div class="pdbe-citations 2gmi" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Ubiquitin--protein ligase]]
[[Category: Carlile CM]]
[[Category: Carlile, C.M.]]
[[Category: Eddins MJ]]
[[Category: Eddins, M.J.]]
[[Category: Gomez KG]]
[[Category: Gomez, K.G.]]
[[Category: Pickart CM]]
[[Category: Pickart, C.M.]]
[[Category: Wolberger C]]
[[Category: Wolberger, C.]]
[[Category: e2]]
[[Category: mms2]]
[[Category: ubc13]]
[[Category: ubc13 ubiquitin covalent complex]]
[[Category: ubiquitin]]
[[Category: uev]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:16:46 2007''

Latest revision as of 09:08, 6 November 2024

Mms2/Ubc13~Ubiquitin

2gmi, resolution 2.50Å

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