6R6H
Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome
Summary for 6R6H
| Entry DOI | 10.2210/pdb6r6h/pdb |
| EMDB information | 4736 |
| Descriptor | COP9 signalosome complex subunit 1, ELOC_HUMAN, RBX1_HUMAN, ... (14 entities in total) |
| Functional Keywords | cullin-ring e3 ligase cop9 signalosome neddylation, ligase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 13 |
| Total formula weight | 455958.20 |
| Authors | Morris, E.P.,Faull, S.V.,Lau, A.M.C.,Politis, A.,Beuron, F.,Cronin, N. (deposition date: 2019-03-27, release date: 2019-08-28, Last modification date: 2024-05-22) |
| Primary citation | Faull, S.V.,Lau, A.M.C.,Martens, C.,Ahdash, Z.,Hansen, K.,Yebenes, H.,Schmidt, C.,Beuron, F.,Cronin, N.B.,Morris, E.P.,Politis, A. Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome. Nat Commun, 10:3814-3814, 2019 Cited by PubMed Abstract: 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. PubMed: 31444342DOI: 10.1038/s41467-019-11772-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (8.4 Å) |
Structure validation
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