FIGURE 2.

The CCT ATPase cycle. (A) Schematic shows the sequential binding of ATP starting with subunits on the CCT2 side of the complex (red) followed by the CCT6 side of the complex (purple). CCT7 and CCT2 first react to and bind nucleotide, followed by the rest of the subunits with increasing ATP. CCT4 (red/white pattern) is the last to bind to ATP and this binding triggers ATP hydrolysis and closing of the ring. CCT3 and CCT6 may load with ATP later in the cycle (delayed release of ADP), while the ADP bound to CCT8 may be exchanged for ATP only under high nucleotide concentrations and/or not involved in ATP consumption. The processing of an unfolded and folded substrate is shown in the gray boxes. ADP (D) is indicated by the yellow heptagon, ATP by the green heptagon, and hydrolyzed ATP: ADP + phosphate (D + P_i) in the dark blue heptagon. The nucleotide-free open ring conformation is based on PDB 4A0O [nucleotide-free (apo) state (Cong et al., 2012)]. The closed ring conformation is based on PDB 6KS6 [Yeast CCT at 0.2 mM ADP-AlFx (Jin et al., 2019)]. The open ring conformation with ADP is based on PDB 4A13 [model refined against symmetry-free cryo-EM map of TRiC-ADP (Cong et al., 2012)].