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http://purl.uniprot.org/citations/31444342http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31444342http://www.w3.org/2000/01/rdf-schema#comment"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."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.org/dc/terms/identifier"doi:10.1038/s41467-019-11772-y"xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Hansen K."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Schmidt C."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Martens C."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Cronin N.B."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Morris E.P."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Beuron F."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Politis A."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Yebenes H."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Faull S.V."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Ahdash Z."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/author"Lau A.M.C."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/name"Nat Commun"xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/pages"3814"xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/title"Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome."xsd:string
http://purl.uniprot.org/citations/31444342http://purl.uniprot.org/core/volume"10"xsd:string
http://purl.uniprot.org/citations/31444342http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31444342
http://purl.uniprot.org/citations/31444342http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/31444342
http://purl.uniprot.org/uniprot/#_A0A024R7W9-mappedCitation-31444342http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31444342
http://purl.uniprot.org/uniprot/#_B4DHR8-mappedCitation-31444342http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31444342
http://purl.uniprot.org/uniprot/#_B2R514-mappedCitation-31444342http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31444342
http://purl.uniprot.org/uniprot/#_Q15369-mappedCitation-31444342http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31444342