Figure 2.

Cryo-EM maps of CAND1-SCF^FBXW7 suggest that CAND1 rolls around an SCF

(A) Cryo-EM maps show CAND1 adopts multiple conformations with its anti-neddylation domain bound, and its anti-SKP1 domain disengaged from SCF^FBXW7. Four maps (a–d) adopt rolling-2 conformations, with CAND1's central arch spiraling away from rather than curling around the SCF. Two maps (a and b) adopt rolling-1 conformations, where only CAND1’s anti-neddylation domain is substantially visible in the density. Other maps show little to no CAND1.

(B) To model the conformations and trajectories of CAND1 bound to SCF^FBXW7, CAND1 domains⁴⁰ were docked into maps for rolling-2 conformations. The full-length CAND1 structure was docked into the density for the anti-neddylation domain in rolling-1a conformation. Alignment of the CAND1 models over the anti-neddylation domain shows twisting and turning of CAND1 HEAT repeats in the different conformations.

(C) To model the conformations and trajectories of CUL1 in CAND1-SCF^FBXW7 complexes, structures CUL1 domains were docked to the maps. Alignment over CUL1’s CR2-CR3 domains shows that the CUL1 WHB, ⍺/β, and CR1 domains assume multiple relative orientations. The orientations in the crystal structure of CAND1-CUL1-RBX1⁴⁰ are shown for reference.

See also Figure S2.