4D0P
Crystal structure of human CSN4
Summary for 4D0P
| Entry DOI | 10.2210/pdb4d0p/pdb |
| Descriptor | COP9 SIGNALOSOME COMPLEX SUBUNIT 4, SODIUM ION, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | signaling protein, pci |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 44578.82 |
| Authors | Bunker, R.D.,Lingaraju, G.M.,Thoma, N.H. (deposition date: 2014-04-29, release date: 2014-07-23, Last modification date: 2024-05-08) |
| Primary citation | Lingaraju, G.M.,Bunker, R.D.,Cavadini, S.,Hess, D.,Hassiepen, U.,Renatus, M.,Fischer, E.S.,Thoma, N.H. Crystal Structure of the Cop9 Signalosome Nature, 512:161-, 2014 Cited by PubMed Abstract: Ubiquitination is a crucial cellular signalling process, and is controlled on multiple levels. Cullin-RING E3 ubiquitin ligases (CRLs) are regulated by the eight-subunit COP9 signalosome (CSN). CSN inactivates CRLs by removing their covalently attached activator, NEDD8. NEDD8 cleavage by CSN is catalysed by CSN5, a Zn(2+)-dependent isopeptidase that is inactive in isolation. Here we present the crystal structure of the entire ∼350-kDa human CSN holoenzyme at 3.8 Å resolution, detailing the molecular architecture of the complex. CSN has two organizational centres: a horseshoe-shaped ring created by its six proteasome lid-CSN-initiation factor 3 (PCI) domain proteins, and a large bundle formed by the carboxy-terminal α-helices of every subunit. CSN5 and its dimerization partner, CSN6, are intricately embedded at the core of the helical bundle. In the substrate-free holoenzyme, CSN5 is autoinhibited, which precludes access to the active site. We find that neddylated CRL binding to CSN is sensed by CSN4, and communicated to CSN5 with the assistance of CSN6, resulting in activation of the deneddylase. PubMed: 25043011DOI: 10.1038/NATURE13566 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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