Figure 5. Schematic mechanism for ClpB catalysed protein disaggregation.

A native protein becomes unfolded or misfolded due to cellular stresses. In the crowded environment of the cell, such (partially) denatured proteins form aggregates. With or without DnaKJE, multiple ClpB hexamers can bind to exposed loops and tails of the aggregates. ClpB hexamers collectively disrupt the aggregate by the combined actions of individual ClpB hexamers tugging and pulling in one or two steps before dissociating. Released from the aggregate, the unfolded intermediates can refold to their native conformations spontaneously or with the assistance of DnaKJE.