Figure 6. Revised model of the TRAP1 ATPase cycle showing the obligatory sequential hydrolysis and conformational switching. .
The protomers are colored teal and gray. The dynamic apo state (upper left) binds two ATPs, which stabilize a strained asymmetric NTD-dimerized closed state. Within this closed state, ATP is hydrolyzed first by the buckled protomer. Release of Pi likely drives the observed conformational switch of the straight protomer (ATP) to a buckled conformation, while the previously buckled protomer (now ADP), straightens. Concomitant with the flip, the client-binding sites (magenta ellipses) are rearranged, to facilitate client remodeling. Now in a buckled conformation, the second ATP is set up to be hydrolyzed. Finally, the ADP/ADP dimer re-opens, releasing nucleotides and resetting TRAP1 to the apo state.