3dqv
From Proteopedia
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| - | [[Image:3dqv.png|left|200px]] | ||
| - | + | ==Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation== | |
| + | <StructureSection load='3dqv' size='340' side='right'caption='[[3dqv]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3dqv]] is a 6 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=3DQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DQV 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]] 3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3dqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dqv OCA], [https://pdbe.org/3dqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dqv RCSB], [https://www.ebi.ac.uk/pdbsum/3dqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dqv ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NEDD8_HUMAN NEDD8_HUMAN] Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.<ref>PMID:10318914</ref> <ref>PMID:10597293</ref> <ref>PMID:11953428</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/dq/3dqv_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3dqv ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cullin-RING ligases (CRLs) comprise the largest ubiquitin E3 subclass, in which a central cullin subunit links a substrate-binding adaptor with an E2-binding RING. Covalent attachment of the ubiquitin-like protein NEDD8 to a conserved C-terminal domain (ctd) lysine stimulates CRL ubiquitination activity and prevents binding of the inhibitor CAND1. Here we report striking conformational rearrangements in the crystal structure of NEDD8~Cul5(ctd)-Rbx1 and SAXS analysis of NEDD8~Cul1(ctd)-Rbx1 relative to their unmodified counterparts. In NEDD8ylated CRL structures, the cullin WHB and Rbx1 RING subdomains are dramatically reoriented, eliminating a CAND1-binding site and imparting multiple potential catalytic geometries to an associated E2. Biochemical analyses indicate that the structural malleability is important for both CRL NEDD8ylation and subsequent ubiquitination activities. Thus, our results point to a conformational control of CRL activity, with ligation of NEDD8 shifting equilibria to disfavor inactive CAND1-bound closed architectures, and favor dynamic, open forms that promote polyubiquitination. | ||
| - | + | Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation.,Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA Cell. 2008 Sep 19;134(6):995-1006. PMID:18805092<ref>PMID:18805092</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3dqv" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
| + | *[[Cullin 3D structures|Cullin 3D structures]] | ||
*[[NEDD8|NEDD8]] | *[[NEDD8|NEDD8]] | ||
| - | + | *[[Ring box protein 3D structures|Ring box protein 3D structures]] | |
| - | == | + | == References == |
| - | < | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Borg | + | [[Category: Large Structures]] |
| - | [[Category: Duda | + | [[Category: Borg LA]] |
| - | [[Category: Hammel | + | [[Category: Duda DM]] |
| - | [[Category: Hunt | + | [[Category: Hammel M]] |
| - | [[Category: Schulman | + | [[Category: Hunt HW]] |
| - | [[Category: Scott | + | [[Category: Schulman BA]] |
| - | + | [[Category: Scott DC]] | |
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Current revision
Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation
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Categories: Homo sapiens | Large Structures | Borg LA | Duda DM | Hammel M | Hunt HW | Schulman BA | Scott DC
