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3o2p

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Revision as of 09:30, 5 August 2016

A Dual E3 Mechanism for Rub1 Ligation to Cdc53: Dcn1(P)-Cdc53(WHB)

Structural highlights

3o2p is a 2 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3o2u, 3o6b
Gene:	DCN1, YLR128W, L3111 (ATCC 18824), CDC53, YDL132W, D2190 (ATCC 18824)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DCN1_YEAST] Required for neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes. Neddylation of cullins play an essential role in the regulation of SCF-type complexes activity. Does not act by preventing deneddylation, but rather facilitates neddylation, possibly by acting with HRT1/RBX1 to recruit the Nedd8-charged E2 UBC12 to the cullin component of SCF-type complexes.^[1] [CDC53_YEAST] Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The SCF complex associates with CDC34 as the E2 ubiquitin-conjugating enzyme. The functional specificity of the SCF complex depends on the type of F-box protein. SCF(CDC4) controls the G1-to-S phase transition; it directs ubiquitination of the phosphorylated CDK inhibitor SIC1 and of CDC6. SCF(CDC4) directs ubiquitination of GCN4. SCF(GRR1) directs ubiquitination of phosphorylated CLN1, CLN2 and GIC2. SCF(MET30) directs ubiquitination of MET4. SCF(DIA2) is specifically involved in the pheromone induced degradation of phosphorylated TEC1. SCF(MDM30) seems to direct ubiquitination of FZ01. Involved in the regulation of methionine biosynthesis genes.^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

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

In ubiquitin-like protein (UBL) cascades, a thioester-linked E2 approximately UBL complex typically interacts with an E3 enzyme for UBL transfer to the target. Here we demonstrate a variant mechanism, whereby the E2 Ubc12 functions with two E3s, Hrt1 and Dcn1, for ligation of the UBL Rub1 to Cdc53's WHB subdomain. Hrt1 functions like a conventional RING E3, with its N terminus recruiting Cdc53 and C-terminal RING activating Ubc12 approximately Rub1. Dcn1's "potentiating neddylation" domain (Dcn1(P)) acts as an additional E3, reducing nonspecific Hrt1-mediated Ubc12 approximately Rub1 discharge and directing Ubc12's active site to Cdc53. Crystal structures of Dcn1(P)-Cdc53(WHB) and Ubc12 allow modeling of a catalytic complex, supported by mutational data. We propose that Dcn1's interactions with both Cdc53 and Ubc12 would restrict the otherwise flexible Hrt1 RING-bound Ubc12 approximately Rub1 to a catalytically competent orientation. Our data reveal mechanisms by which two E3s function synergistically to promote UBL transfer from one E2 to a target.

A dual E3 mechanism for Rub1 ligation to Cdc53.,Scott DC, Monda JK, Grace CR, Duda DM, Kriwacki RW, Kurz T, Schulman BA Mol Cell. 2010 Sep 10;39(5):784-96. PMID:20832729^[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kurz T, Ozlu N, Rudolf F, O'Rourke SM, Luke B, Hofmann K, Hyman AA, Bowerman B, Peter M. The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C. elegans and S. cerevisiae. Nature. 2005 Jun 30;435(7046):1257-61. PMID:15988528 doi:http://dx.doi.org/nature03662
↑ Kornitzer D, Raboy B, Kulka RG, Fink GR. Regulated degradation of the transcription factor Gcn4. EMBO J. 1994 Dec 15;13(24):6021-30. PMID:7813440
↑ Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell. 1997 Oct 17;91(2):209-19. PMID:9346238
↑ Feldman RM, Correll CC, Kaplan KB, Deshaies RJ. A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell. 1997 Oct 17;91(2):221-30. PMID:9346239
↑ Drury LS, Perkins G, Diffley JF. The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast. EMBO J. 1997 Oct 1;16(19):5966-76. PMID:9312054 doi:10.1093/emboj/16.19.5966
↑ Jaquenoud M, Gulli MP, Peter K, Peter M. The Cdc42p effector Gic2p is targeted for ubiquitin-dependent degradation by the SCFGrr1 complex. EMBO J. 1998 Sep 15;17(18):5360-73. PMID:9736614 doi:10.1093/emboj/17.18.5360
↑ Patton EE, Willems AR, Sa D, Kuras L, Thomas D, Craig KL, Tyers M. Cdc53 is a scaffold protein for multiple Cdc34/Skp1/F-box proteincomplexes that regulate cell division and methionine biosynthesis in yeast. Genes Dev. 1998 Mar 1;12(5):692-705. PMID:9499404
↑ Skowyra D, Koepp DM, Kamura T, Conrad MN, Conaway RC, Conaway JW, Elledge SJ, Harper JW. Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. Science. 1999 Apr 23;284(5414):662-5. PMID:10213692
↑ Koepp DM, Kile AC, Swaminathan S, Rodriguez-Rivera V. The F-box protein Dia2 regulates DNA replication. Mol Biol Cell. 2006 Apr;17(4):1540-8. Epub 2006 Jan 18. PMID:16421250 doi:http://dx.doi.org/E05-09-0884
↑ Scott DC, Monda JK, Grace CR, Duda DM, Kriwacki RW, Kurz T, Schulman BA. A dual E3 mechanism for Rub1 ligation to Cdc53. Mol Cell. 2010 Sep 10;39(5):784-96. PMID:20832729 doi:10.1016/j.molcel.2010.08.030

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3o2p"

@@ Line 1: / Line 1: @@
 ==A Dual E3 Mechanism for Rub1 Ligation to Cdc53: Dcn1(P)-Cdc53(WHB)==
 <StructureSection load='3o2p' size='340' side='right' caption='[[3o2p]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3o2p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O2P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3o2p]] is a 2 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=3O2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O2P FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3o2u|3o2u]], [[3o6b|3o6b]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCN1, YLR128W, L3111 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), CDC53, YDL132W, D2190 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCN1, YLR128W, L3111 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), CDC53, YDL132W, D2190 ([http://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=3o2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o2p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o2p RCSB], [http://www.ebi.ac.uk/pdbsum/3o2p PDBsum]</span></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=3o2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o2p OCA], [http://pdbe.org/3o2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o2p RCSB], [http://www.ebi.ac.uk/pdbsum/3o2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o2p ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=3o2p ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3o2p" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cullin|Cullin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Saccharomyces cerevisiae]]
+[[Category: Atcc 18824]]
 [[Category: Duda, D M]]
 [[Category: Grace, C R.R]]

3o2p

From Proteopedia

Revision as of 09:30, 5 August 2016

A Dual E3 Mechanism for Rub1 Ligation to Cdc53: Dcn1(P)-Cdc53(WHB)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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