Sequential allosteric mechanism of ATP hydrolysis by the CCT/TRiC chaperone is revealed through Arrhenius analysis

Significance Many biological machines consist of oligomeric rings that undergo conformational changes driven by ATP binding and hydrolysis. These conformational changes can take place in a concerted, probabilistic, or sequential fashion. Knowing the mode of conformational switching is important for understanding how these machines work. Here, we show that measuring the temperature dependence of the ATPase reaction of the chaperonin CCT/TRiC provides insight into its mode of switching. Our results show that ATP hydrolysis triggers sequential ‟conformational waves” in CCT/TRiC that proceed both clockwise and counterclockwise around its rings. Knowing the mechanism of allosteric switching is important for understanding how molecular machines work. The CCT/TRiC chaperonin nanomachine undergoes ATP-driven conformational changes that are crucial for its folding function. Here, we demonstrate that insight into its allosteric mechanism of ATP hydrolysis can be achieved by Arrhenius analysis. Our results show that ATP hydrolysis triggers sequential ‟conformational waves.” They also suggest that these waves start from subunits CCT6 and CCT8 (or CCT3 and CCT6) and proceed clockwise and counterclockwise, respectively.

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