Figure 2. Cryo EM structure representing neddylated CRL1^β-TRCP-mediated ubiquitin transfer from UBE2D to IκBα substrate.

a, Cryo EM density representing neddylated CRL1^β-TRCP-UBE2D~ubiquitin-IκBα substrate intermediate, wherein UBE2D~ubiquitin is activated and juxtaposed with substrate. b, The substrate scaffolding module connects β-TRCP-bound substrate to the intermolecular cullin-RBX (C/R) domain. c, The catalytic module consists of RBX1’s RING-UBE2D~UB in the canonical closed activated conformation, and additional density corresponding to the chemical surrogate for substrate undergoing ubiquitylation. d, NEDD8 and its covalently-linked CUL1 WHB domain form the activation module.