Extended Data Figure 8: CSN5 autoinhibition in the CSN holoenzyme and isolated CSN5.

a, Cartoon representation of the active site of isolated CSN5 (PDB accession 4F7O)²². b, A cullin Lys-NEDD8 isopeptide conjugate modelled in the isolated CSN5 active site (see Fig. 4d). c, Superposition of the CSN5 Ins-1 loop conformations in CSN (cyan) and isolated CSN5 (cream). d, Active site of the zinc metalloprotease, pro-astacin (PDB accession 3LQ0)⁷⁰, showing the zinc coordinating and active site residues (green), and the autoinhibitory residue, Asp 21, from its pro-region in sticks (orange). e, Removal of the pro-region bearing Asp 21 produces catalytically active astacin (PDB accession 1AST⁷¹). f, Structure-based sequence alignment (PROMALS3D⁷²) of the JAMM motif region in CSN5 and its 19S lid paralogue, RPN11.