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==Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation==
==Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation==
<StructureSection load='3dqv' size='340' side='right' caption='[[3dqv]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
<StructureSection load='3dqv' size='340' side='right'caption='[[3dqv]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3dqv]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DQV FirstGlance]. <br>
<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NEDD8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CUL5, VACM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RBX1, RNF75, ROC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
<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=3dqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dqv OCA], [http://pdbe.org/3dqv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dqv RCSB], [http://www.ebi.ac.uk/pdbsum/3dqv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dqv ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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> [[http://www.uniprot.org/uniprot/RBX1_HUMAN RBX1_HUMAN]] E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair. The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme, like CDC34, to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.<ref>PMID:10579999</ref> <ref>PMID:11027288</ref> <ref>PMID:16751180</ref> <ref>PMID:16678110</ref> <ref>PMID:19679664</ref>  [[http://www.uniprot.org/uniprot/CUL5_HUMAN CUL5_HUMAN]] Core component of multiple SCF-like ECS (Elongin-Cullin 2/5-SOCS-box protein) 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 functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAk2. Seems to be involved poteosomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. May form a cell surface vasopressin receptor.
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dq/3dqv_consurf.spt"</scriptWhenChecked>
     <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/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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==See Also==
==See Also==
*[[Cullin|Cullin]]
*[[Cullin 3D structures|Cullin 3D structures]]
*[[NEDD8|NEDD8]]
*[[NEDD8|NEDD8]]
*[[RING box protein|RING box protein]]
*[[Ring box protein 3D structures|Ring box protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Borg, L A]]
[[Category: Large Structures]]
[[Category: Duda, D M]]
[[Category: Borg LA]]
[[Category: Hammel, M]]
[[Category: Duda DM]]
[[Category: Hunt, H W]]
[[Category: Hammel M]]
[[Category: Schulman, B A]]
[[Category: Hunt HW]]
[[Category: Scott, D C]]
[[Category: Schulman BA]]
[[Category: Acetylation]]
[[Category: Scott DC]]
[[Category: Cullin]]
[[Category: Cullin-ring ligase]]
[[Category: Cytoplasm]]
[[Category: Dna damage]]
[[Category: Dna repair]]
[[Category: Host-virus interaction]]
[[Category: Ligase]]
[[Category: Metal-binding]]
[[Category: Nedd8]]
[[Category: Nucleus]]
[[Category: Receptor]]
[[Category: Scf]]
[[Category: Signaling protein]]
[[Category: Ubiquitin]]
[[Category: Ubl conjugation]]
[[Category: Ubl conjugation pathway]]
[[Category: Zinc]]
[[Category: Zinc-finger]]
Retrieved from "https://proteopedia.org/3dqv"