View source for 9qo3


==Dissociation-state-2 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex==
<StructureSection load='9qo3' size='340' side='right'caption='[[9qo3]], [[Resolution|resolution]] 4.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qo3]] is a 10 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=9QO3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QO3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</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=9qo3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qo3 OCA], [https://pdbe.org/9qo3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qo3 RCSB], [https://www.ebi.ac.uk/pdbsum/9qo3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qo3 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cullin-RING ligases (CRLs) are the largest family of E3 ligases, with ubiquitination activity dynamically regulated by neddylation and deneddylation by the COP9 signalosome (CSN). CSN-mediated deneddylation not only deactivates CRLs but also enables substrate receptor exchange. Although CSN is a promising drug target, the structural basis underlying its catalytic mechanism remains unclear. Here, we use cryo-electron microscopy (cryo-EM) to uncover distinct functional states of CSN-CRL (SCF) complexes, capturing key intermediates of the deneddylation cycle. We visualise an autoinhibited docking state and a catalytic intermediate in which CSN5 Ins-1 loop, RBX1 RING and neddylated Cullin WHB domains are repositioned for isopeptide cleavage. We further resolve four dissociation intermediates that define the stepwise release of CSN from its product, with RBX1 RING stabilising key interactions. Additionally, our structures locate CSNAP within a CSN3-CSN8 groove. Together, our study provides a mechanistic model for CSN function and informs the rational design of CSN-targeted therapeutics.

Structural basis of CSN-mediated SCF deneddylation.,Ding S, Clapperton JA, Maeots ME, Kunzelmann S, Shaaban M, Enchev RI Nat Commun. 2026 Jan 23;17(1):951. doi: 10.1038/s41467-025-67566-y. PMID:41577659<ref>PMID:41577659</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qo3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Clapperton JA]]
[[Category: Ding S]]
[[Category: Enchev RI]]
[[Category: Maeots ME]]