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==Crystal structure of ubiquitin-conjugating enzyme E2-25kDa (Huntington interacting protein 2) M172A mutant== | ==Crystal structure of ubiquitin-conjugating enzyme E2-25kDa (Huntington interacting protein 2) M172A mutant== | ||
<StructureSection load='3e46' size='340' side='right' caption='[[3e46]], [[Resolution|resolution]] 1.86Å' scene=''> | <StructureSection load='3e46' size='340' side='right'caption='[[3e46]], [[Resolution|resolution]] 1.86Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3e46]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3e46]] 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=3E46 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E46 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e46 OCA], [https://pdbe.org/3e46 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e46 RCSB], [https://www.ebi.ac.uk/pdbsum/3e46 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e46 ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/UBE2K_HUMAN UBE2K_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1.<ref>PMID:8702625</ref> <ref>PMID:10634809</ref> <ref>PMID:10675012</ref> <ref>PMID:16714285</ref> <ref>PMID:16868077</ref> <ref>PMID:17873885</ref> <ref>PMID:20061386</ref> <ref>PMID:19906396</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e4/3e46_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e4/3e46_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=3e46 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 29: | Line 28: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3e46" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[ | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 37: | Line 37: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Flatt | [[Category: Flatt JW]] | ||
[[Category: Hughes | [[Category: Hughes RC]] | ||
[[Category: Meehan | [[Category: Meehan EJ]] | ||
[[Category: Ng | [[Category: Ng JD]] | ||
[[Category: Twigg | [[Category: Twigg PD]] | ||
[[Category: Wilson | [[Category: Wilson RC]] | ||
Latest revision as of 15:58, 30 August 2023
Crystal structure of ubiquitin-conjugating enzyme E2-25kDa (Huntington interacting protein 2) M172A mutantCrystal structure of ubiquitin-conjugating enzyme E2-25kDa (Huntington interacting protein 2) M172A mutant
Structural highlights
FunctionUBE2K_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1.[1] [2] [3] [4] [5] [6] [7] [8] 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 PubMedThe ubiquitin-conjugating enzyme E2-25K has been identified as a huntingtin (the key protein in Huntington's disease) interacting protein and has been shown to play a role in mediating the toxicity of Abeta, the principal protein involved in Alzheimer's disease pathogenesis. E2-25K is a dual-domain protein with an ubiquitin-associated (UBA) domain as well as a conserved ubiquitin-conjugating (UBC) domain which catalyzes the formation of a covalent bond between the C-terminal glycine of an ubiquitin molecule and the -amine of a lysine residue on the acceptor protein as part of the ubiquitin-proteasome pathway. The crystal structures of E2-25K M172A mutant protein at pH 6.5 and pH 8.5 were determined to 1.9 and 2.2 A resolution, respectively. Examination of the structures revealed domain-domain interactions between the UBC and UBA domains which have not previously been reported. Structure of full-length ubiquitin-conjugating enzyme E2-25K (huntingtin-interacting protein 2).,Wilson RC, Hughes RC, Flatt JW, Meehan EJ, Ng JD, Twigg PD Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 May 1;65(Pt, 5):440-4. Epub 2009 Apr 24. PMID:19407372[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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