4d0p
From Proteopedia
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==Crystal structure of human CSN4== | ==Crystal structure of human CSN4== | ||
- | <StructureSection load='4d0p' size='340' side='right' caption='[[4d0p]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='4d0p' size='340' side='right'caption='[[4d0p]], [[Resolution|resolution]] 1.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>[[4d0p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D0P OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4d0p]] is a 1 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=4D0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4D0P FirstGlance]. <br> |
- | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>< | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
- | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
- | <table> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4d0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d0p OCA], [https://pdbe.org/4d0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4d0p RCSB], [https://www.ebi.ac.uk/pdbsum/4d0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4d0p ProSAT]</span></td></tr> |
+ | </table> | ||
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/CSN4_HUMAN CSN4_HUMAN] Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. Also involved in the deneddylation of non-cullin subunits such as STON2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, IRF8/ICSBP and SNAPIN, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively.<ref>PMID:9535219</ref> <ref>PMID:11285227</ref> <ref>PMID:11337588</ref> <ref>PMID:12732143</ref> <ref>PMID:12628923</ref> <ref>PMID:21102408</ref> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Ubiquitination is a crucial cellular signalling process, and is controlled on multiple levels. Cullin-RING E3 ubiquitin ligases (CRLs) are regulated by the eight-subunit COP9 signalosome (CSN). CSN inactivates CRLs by removing their covalently attached activator, NEDD8. NEDD8 cleavage by CSN is catalysed by CSN5, a Zn2+-dependent isopeptidase that is inactive in isolation. Here we present the crystal structure of the entire approximately 350-kDa human CSN holoenzyme at 3.8 A resolution, detailing the molecular architecture of the complex. CSN has two organizational centres: a horseshoe-shaped ring created by its six proteasome lid-CSN-initiation factor 3 (PCI) domain proteins, and a large bundle formed by the carboxy-terminal alpha-helices of every subunit. CSN5 and its dimerization partner, CSN6, are intricately embedded at the core of the helical bundle. In the substrate-free holoenzyme, CSN5 is autoinhibited, which precludes access to the active site. We find that neddylated CRL binding to CSN is sensed by CSN4, and communicated to CSN5 with the assistance of CSN6, resulting in activation of the deneddylase. | ||
+ | |||
+ | Crystal structure of the human COP9 signalosome.,Lingaraju GM, Bunker RD, Cavadini S, Hess D, Hassiepen U, Renatus M, Fischer ES, Thoma NH Nature. 2014 Jul 16. doi: 10.1038/nature13566. PMID:25043011<ref>PMID:25043011</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 4d0p" style="background-color:#fffaf0;"></div> | ||
+ | |||
+ | ==See Also== | ||
+ | *[[Signalosome|Signalosome]] | ||
+ | == References == | ||
+ | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
- | [[Category: | + | [[Category: Homo sapiens]] |
- | [[Category: | + | [[Category: Large Structures]] |
- | [[Category: | + | [[Category: Bunker RD]] |
- | [[Category: | + | [[Category: Lingaraju GM]] |
- | [[Category: | + | [[Category: Thoma NH]] |
Current revision
Crystal structure of human CSN4
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