Fig. 6: Refined model of HtpG’s client chaperoning functional cycle.
From: The dynamic triage interplay of Hsp90 with its chaperone cycle and client binding
HtpG initially captures the client in its open state, engaging unfolded proteins with one hydrophobic groove on each protomer simultaneously. ATP binding modulates HtpG’s conformational equilibrium, promoting a shift towards closure while it remains in a polymorphic state that samples multiple conformations. ATP hydrolysis induces a substantial conformational shift in HtpG, stabilizing it in a distinct, ‘compact’ state, followed by ADP release which resets the chaperone to its nucleotide-free state. Throughout its cycle, HtpG exhibits distinct dynamic signatures associated with different nucleotide states, illustrated with varying background colors in the figure. This model underscores the dual role of HtpG’s ATPase activity in mechanically manipulating clients and precisely regulating molecular dynamics to optimize chaperone function.
