Structure-based model for the ATPase cycle in PAN-proteasomes. (A) Cartoon representations of the five ATPase states identified, along with a putative state hypothesized (hypothetical state). In each state, the subunit in the highest and lowest positions is indicated with colored H and L, respectively, and the active (ADP) pocket is indicated by asterisks. (B) Putative scheme of the conformational changes that drive the ATPase cycle around the AAA ring. ATP hydrolysis in the active pocket causes withdrawal of the ISS loop, and upward movement of pore helices. Detachment of ISS contact signals the counterclockwise adjacent subunit to hydrolyze ATP.