ATPases substrate unfolding

The binding of ubiquitinylated substrates requires the 19S complex of the proteasome, which possesses a ubiquitin binding site and several ATPase sites. It is assumed that the recognition and ATP-dependent unfolding of the substrate protein occurs within the 19S complex. 

Protein unfolding is very likely a general mechanism used by Clp ATPases to carry out their other biological roles in addition to translocation of substrates to proteases. Although it is not a prerequisite that a protein be globally unfolded to be remodeled, very likely RepA dimers,... 

Although much has been learned about the structure and function of Clp chaperones and their role in proteolysis, the mechanism of protein unfolding catalyzed by Clp ATPases and the mechanism of translocation of the unfolded proteins from Clp ATPases to partner proteases remain unsolved puzzles. However, models in which mechanical force is used to destabilize the structure of the substrate in a processive and directional manner are probable. It also seems likely that when ClpA ATPases are associated with proteases, unfolding is coupled to extrusion of the unfolded protein into the proteolytic cavity. In summary, it is anticipated that the large family of Clp ATPases will accomplish their many important cellular functions by similar mechanisms and what has been learned by studying the prokaryotic members reviewed here will shed a great deal of light on all members of the family. 

---