View source for 4wsn


==Crystal structure of the COP9 signalosome, a P1 crystal form==
<StructureSection load='4wsn' size='340' side='right'caption='[[4wsn]], [[Resolution|resolution]] 5.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wsn]] is a 48 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=4WSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WSN 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]] 5.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=4wsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wsn OCA], [https://pdbe.org/4wsn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wsn RCSB], [https://www.ebi.ac.uk/pdbsum/4wsn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wsn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CSN1_HUMAN CSN1_HUMAN] Essential 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. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, 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. Suppresses G-protein- and mitogen-activated protein kinase-mediated signal transduction.<ref>PMID:9535219</ref> <ref>PMID:11285227</ref> <ref>PMID:11337588</ref> <ref>PMID:12732143</ref> <ref>PMID:12628923</ref> 
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== Publication Abstract from PubMed ==
The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A(DDB2)) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A(DBB2) is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A(DDB2) and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 A resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN.

Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome.,Cavadini S, Fischer ES, Bunker RD, Potenza A, Lingaraju GM, Goldie KN, Mohamed WI, Faty M, Petzold G, Beckwith RE, Tichkule RB, Hassiepen U, Abdulrahman W, Pantelic RS, Matsumoto S, Sugasawa K, Stahlberg H, Thoma NH Nature. 2016 Mar 31;531(7596):598-603. doi: 10.1038/nature17416. PMID:27029275<ref>PMID:27029275</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4wsn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Signalosome|Signalosome]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bunker RD]]
[[Category: Lingaraju GM]]
[[Category: Thoma NH]]