6r7h

Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome

Loading... Status: waiting for Mol* initialization Structural highlights 6r7h is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 8.8Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. Publication Abstract from PubMed Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members. Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome.,Faull SV, Lau AMC, Martens C, Ahdash Z, Hansen K, Yebenes H, Schmidt C, Beuron F, Cronin NB, Morris EP, Politis A Nat Commun. 2019 Aug 23;10(1):3814. doi: 10.1038/s41467-019-11772-y. PMID:31444342 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cullin 3D structures Elongation factor 3D structures Signalosome

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