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| | ==Structure of the yeast U-box-containing ubiquitin ligase Ufd2p== | | ==Structure of the yeast U-box-containing ubiquitin ligase Ufd2p== |
| - | <StructureSection load='2qiz' size='340' side='right' caption='[[2qiz]], [[Resolution|resolution]] 2.56Å' scene=''> | + | <StructureSection load='2qiz' size='340' side='right'caption='[[2qiz]], [[Resolution|resolution]] 2.56Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qiz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QIZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QIZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qiz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QIZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qj0|2qj0]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qj0|2qj0]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UFD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UFD2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qiz OCA], [http://pdbe.org/2qiz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qiz RCSB], [http://www.ebi.ac.uk/pdbsum/2qiz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qiz ProSAT]</span></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=2qiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qiz OCA], [https://pdbe.org/2qiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qiz RCSB], [https://www.ebi.ac.uk/pdbsum/2qiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qiz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UFD2_YEAST UFD2_YEAST]] E4 ubiquitin chain-elongation enzyme specifically involved in polyubiquitin chain assembly. Binds to CDC48 and elongates mono- and diubiquitinated ERAD substrates presented by the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex to a chain length of 4 to 6 ubiquitin moieties. Delivers these polyubiquitinated substrates to RAD23 and DSK2, which target them to the proteasome. Has E3 ubiquitin-protein ligase activity, accepting ubiquitin from its cognate E2 ubiquitin-conjugating enzyme UBC4. Enhances ubiquitination at 'Lys-48', but not at 'Lys-29' of the Ub moiety. Promotes ubiquitin chain elongation at 'Lys-48' on the DOA10 substrate PEX29. Also involved in the proteolytic processing of the ER-bound transcription factor SPT23.<ref>PMID:10089879</ref> <ref>PMID:15240124</ref> <ref>PMID:15652483</ref> <ref>PMID:18191224</ref> <ref>PMID:20159987</ref> | + | [[https://www.uniprot.org/uniprot/UFD2_YEAST UFD2_YEAST]] E4 ubiquitin chain-elongation enzyme specifically involved in polyubiquitin chain assembly. Binds to CDC48 and elongates mono- and diubiquitinated ERAD substrates presented by the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex to a chain length of 4 to 6 ubiquitin moieties. Delivers these polyubiquitinated substrates to RAD23 and DSK2, which target them to the proteasome. Has E3 ubiquitin-protein ligase activity, accepting ubiquitin from its cognate E2 ubiquitin-conjugating enzyme UBC4. Enhances ubiquitination at 'Lys-48', but not at 'Lys-29' of the Ub moiety. Promotes ubiquitin chain elongation at 'Lys-48' on the DOA10 substrate PEX29. Also involved in the proteolytic processing of the ER-bound transcription factor SPT23.<ref>PMID:10089879</ref> <ref>PMID:15240124</ref> <ref>PMID:15652483</ref> <ref>PMID:18191224</ref> <ref>PMID:20159987</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Atcc 18824]] | | [[Category: Atcc 18824]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Brunger, A T]] | | [[Category: Brunger, A T]] |
| | [[Category: Tu, D]] | | [[Category: Tu, D]] |
| | [[Category: Helical hairpin]] | | [[Category: Helical hairpin]] |
| | [[Category: Ligase]] | | [[Category: Ligase]] |
| Structural highlights
Function
[UFD2_YEAST] E4 ubiquitin chain-elongation enzyme specifically involved in polyubiquitin chain assembly. Binds to CDC48 and elongates mono- and diubiquitinated ERAD substrates presented by the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex to a chain length of 4 to 6 ubiquitin moieties. Delivers these polyubiquitinated substrates to RAD23 and DSK2, which target them to the proteasome. Has E3 ubiquitin-protein ligase activity, accepting ubiquitin from its cognate E2 ubiquitin-conjugating enzyme UBC4. Enhances ubiquitination at 'Lys-48', but not at 'Lys-29' of the Ub moiety. Promotes ubiquitin chain elongation at 'Lys-48' on the DOA10 substrate PEX29. Also involved in the proteolytic processing of the ER-bound transcription factor SPT23.[1] [2] [3] [4] [5]
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 PubMed
Proteins conjugated by Lys-48-linked polyubiquitin chains are preferred substrates of the eukaryotic proteasome. Polyubiquitination requires an activating enzyme (E1), a conjugating enzyme (E2), and a ligase (E3). Occasionally, these enzymes only assemble short ubiquitin oligomers, and their extension to full length involves a ubiquitin elongating factor termed E4. Ufd2p, as the first E4 identified to date, is involved in the degradation of misfolded proteins of the endoplasmic reticulum and of a ubiquitin-beta-GAL fusion substrate in Saccharomyces cerevisiae. The mechanism of action of Ufd2p is unknown. Here we describe the crystal structure of the full-length yeast Ufd2p protein. Ufd2p has an elongated shape consisting of several irregular Armadillo-like repeats with two helical hairpins protruding from it and a U-box domain flexibly attached to its C terminus. The U-box of Ufd2p has a fold similar to that of the RING (Really Interesting New Gene) domain that is present in certain ubiquitin ligases. Accordingly, Ufd2p has all of the hallmarks of a RING finger-containing ubiquitin ligase: it associates with its cognate E2 Ubc4p via its U-box domain and catalyzes the transfer of ubiquitin from the E2 active site to Ufd2p itself or to an acceptor ubiquitin molecule to form unanchored diubiquitin oligomers. Thus, Ufd2p can function as a bona fide E3 ubiquitin ligase to promote ubiquitin chain elongation on a substrate.
Inaugural Article: Structure and function of the yeast U-box-containing ubiquitin ligase Ufd2p.,Tu D, Li W, Ye Y, Brunger AT Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15599-606. Epub 2007 Sep 21. PMID:17890322[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Koegl M, Hoppe T, Schlenker S, Ulrich HD, Mayer TU, Jentsch S. A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell. 1999 Mar 5;96(5):635-44. PMID:10089879
- ↑ Saeki Y, Tayama Y, Toh-e A, Yokosawa H. Definitive evidence for Ufd2-catalyzed elongation of the ubiquitin chain through Lys48 linkage. Biochem Biophys Res Commun. 2004 Jul 30;320(3):840-5. PMID:15240124 doi:10.1016/j.bbrc.2004.05.216
- ↑ Richly H, Rape M, Braun S, Rumpf S, Hoege C, Jentsch S. A series of ubiquitin binding factors connects CDC48/p97 to substrate multiubiquitylation and proteasomal targeting. Cell. 2005 Jan 14;120(1):73-84. PMID:15652483 doi:10.1016/j.cell.2004.11.013
- ↑ Nakatsukasa K, Huyer G, Michaelis S, Brodsky JL. Dissecting the ER-associated degradation of a misfolded polytopic membrane protein. Cell. 2008 Jan 11;132(1):101-12. doi: 10.1016/j.cell.2007.11.023. PMID:18191224 doi:10.1016/j.cell.2007.11.023
- ↑ Liu C, van Dyk D, Xu P, Choe V, Pan H, Peng J, Andrews B, Rao H. Ubiquitin chain elongation enzyme Ufd2 regulates a subset of Doa10 substrates. J Biol Chem. 2010 Apr 2;285(14):10265-72. Epub 2010 Feb 16. PMID:20159987 doi:M110.110551
- ↑ Tu D, Li W, Ye Y, Brunger AT. Inaugural Article: Structure and function of the yeast U-box-containing ubiquitin ligase Ufd2p. Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15599-606. Epub 2007 Sep 21. PMID:17890322
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