Fig. 5. Model of conformational changes in the client-engaged mtHsp60 reaction cycle.

State 1: Apical domains (pink) of mtHsp60^apo heptamers are flexible, and exhibit modest rotation about the apical-intermediate hinge, denoted by coloration of helices H and I. State 2: Client binding to mtHsp60^apo preserves apical domain asymmetry, and client can localize to multiple depths of the heptamer, facilitated by mtHsp60 apical domains and the flexible C-terminal tails. State 3: ATP binding induces the dimerization of heptamers through the equatorial domains and a more pronounced apical domain asymmetry in an alternating up/down arrangement. Helices H and I in ‘down’ protomers (red) contact client, while those in ‘up’ protomers (green) are competent to bind mtHsp10. State 3a: mtHsp10 initially binds the mtHsp60 heptamer using the three upward-facing apical domains; all apical domains then transition to the conformation observed in the mtHsp10-bound complex (state 4). After ATP hydrolysis and client folding (state 5), client, mtHsp10, and ADP are released, and the double-ring complex disassociates into heptamers.