Figure 8. Model for the conformational cycle and unique energy landscape of TRAP1.
(A) In the absence of nucleotide the chaperone is in equilibrium between various open conformations (for simplicity we only show the most open) with the strap folded back onto the cis protomer. Upon binding of ATP, conformational changes necessary for the transition to the closed state are initiated. Here, we propose that the cis contacts of the strap are broken allowing the lid and NTD to undergo conformational changes towards the closed state. After the slow closure step the chaperone assumes the previously reported asymmetric conformation (Lavery et al., 2014). Sequential hydrolysis leads to changes in symmetry rearranging the unique MD:CTD interfaces and client binding residues (red) before sampling the ADP conformation and resetting the cycle to the apo state equilibrium. (B) Model for the unique energy landscape of TRAP1. Solid lines illustrate the energy landscape of WT TRAP1, and the dashed lines depict the change in landscape upon the loss of the extended N-terminal strap sequence in TRAP1. By stabilizing both the apo and closed states, the strap increases the effective height of the energy barrier. This modulates the conformational landscape, and in the case of hTRAP1 provides pronounced temperature sensitivity.