Extended Data Fig. 7: Conformational changes in CRL4^CSA upon neddylation and comparison to cullin 1.

a. Schematic representation of ubiquitylation modules in C^NRL4^CSA-E2-Ub according to the classification in³⁷. b. Cryo-EM maps and a ribbon model of the substrate scaffolding module. c. Cryo-EM maps and a ribbon model of the catalytic module. d. Cryo-EM maps and a ribbon model of the activation module. e. Zoom-in on the interface between the substrate scaffolding and the catalytic module. Prominent R92 is inserted in the hydrophobic interface between CSA and UBCH5B. f. Zoom-in on the interface between the substrate scaffolding and the activating module. The interface is dominated by many complementary charged interactions. g. Conformational changes induced by neddylation. The helix connecting C/R and WHB ___domain unfolds to allow repositioning of NEDD8-bound WHB (left). Neddylation also induces dramatic repositioning of RBX1 RING (right). h. Conformational changes upon neddylation of CUL4A are almost identical to the changes in CUL1, suggesting a conserved mechanism of CRL activation by neddylation. The structure solved in this work was compared to the structure of C^NRL1^ß-TRCP (PDB: 6TTU)³⁷.