3o2p: Difference between revisions
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==A Dual E3 Mechanism for Rub1 Ligation to Cdc53: Dcn1(P)-Cdc53(WHB)== | |||
<StructureSection load='3o2p' size='340' side='right'caption='[[3o2p]], [[Resolution|resolution]] 2.23Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3o2p]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=3O2P 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]] 2.233Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=3o2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o2p OCA], [https://pdbe.org/3o2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o2p RCSB], [https://www.ebi.ac.uk/pdbsum/3o2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o2p ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DCN1_YEAST 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.<ref>PMID:15988528</ref> | |||
== 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/o2/3o2p_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3o2p ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:20832729</ref> | |||
From MEDLINE®/PubMed®, 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 3D structures|Cullin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae]] | |||
[[Category: Duda DM]] | |||
[[Category: Grace CRR]] | |||
[[Category: Kriwacki RW]] | |||
[[Category: Kurz T]] | |||
[[Category: Monda JK]] | |||
[[Category: Schulman BA]] | |||
[[Category: Scott DC]] | |||
Latest revision as of 12:26, 6 September 2023
A Dual E3 Mechanism for Rub1 Ligation to Cdc53: Dcn1(P)-Cdc53(WHB)A Dual E3 Mechanism for Rub1 Ligation to Cdc53: Dcn1(P)-Cdc53(WHB)
Structural highlights
FunctionDCN1_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] 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 PubMedIn 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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