Model proposed to explain the benefits that the association equilibrium of DNAJA2 could have in the holding and substrate remodelling activities of the Hsc70 system. Under heat shock (stress) conditions, DNAJA2 oligomers dissociate into smaller species with the client binding sites exposed to complex unfolded client proteins, and therefore with an enhanced holding activity. The height within the triangle reflects the abundance of the corresponding oligomerization states. Once the physiological conditions are restored the cochaperone-substrate protein complex might associate into large oligomers. The array of nearby JDs in the oligomer could act as a scaffold, allowing simultaneous binding of several Hsc70 molecules to the chaperone-bound, unfolded client for an efficient substrate remodelling. The conformational cycle of bound Hsc70 molecules, driven by ATP hydrolysis, that is necessary for substrate remodelling would dissociate the DNAJA2 assembly, releasing free DNAJA2 dimers that could reassociate to start the cycle.
