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3m63

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Revision as of 18:23, 25 December 2014

Crystal structure of Ufd2 in complex with the ubiquitin-like (UBL) domain of Dsk2

Structural highlights

3m63 is a 2 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3m62
Gene:	D1255, UFD2, YDL190C (Saccharomyces cerevisiae), DSK2, SHE4, YM8021.02, YMR276W (Saccharomyces cerevisiae)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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 containing ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains interact with various binding partners and function as hubs during ubiquitin-mediated protein degradation. A common interaction of the budding yeast UBL-UBA proteins Rad23 and Dsk2 with the E4 ubiquitin ligase Ufd2 has been described in endoplasmic reticulum-associated degradation among other pathways. The UBL domains of Rad23 and Dsk2 play a prominent role in this process by interacting with Ufd2 and different subunits of the 26 S proteasome. Here, we report crystal structures of Ufd2 in complex with the UBL domains of Rad23 and Dsk2. The N-terminal UBL-interacting region of Ufd2 exhibits a unique sequence pattern, which is distinct from any known ubiquitin- or UBL-binding domain identified so far. Residue-specific differences exist in the interactions of these UBL domains with Ufd2, which are coupled to subtle differences in their binding affinities. The molecular details of their differential interactions point to a role for adaptive evolution in shaping these interfaces.

The yeast E4 ubiquitin ligase Ufd2 interacts with the ubiquitin-like domains of Rad23 and Dsk2 via a novel and distinct ubiquitin-like binding domain.,Hanzelmann P, Stingele J, Hofmann K, Schindelin H, Raasi S J Biol Chem. 2010 Jun 25;285(26):20390-8. Epub 2010 Apr 28. PMID:20427284^[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
↑ Hanzelmann P, Stingele J, Hofmann K, Schindelin H, Raasi S. The yeast E4 ubiquitin ligase Ufd2 interacts with the ubiquitin-like domains of Rad23 and Dsk2 via a novel and distinct ubiquitin-like binding domain. J Biol Chem. 2010 Jun 25;285(26):20390-8. Epub 2010 Apr 28. PMID:20427284 doi:10.1074/jbc.M110.112532

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3m63"

@@ Line 8: / Line 8: @@
 <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=3m63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m63 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3m63 RCSB], [http://www.ebi.ac.uk/pdbsum/3m63 PDBsum]</span></td></tr>
 </table>
+== 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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3m63

From Proteopedia

Revision as of 18:23, 25 December 2014

Crystal structure of Ufd2 in complex with the ubiquitin-like (UBL) domain of Dsk2

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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