Reference: Mogk A, et al. (2008) Common and specific mechanisms of AAA+ proteins involved in protein quality control. Biochem Soc Trans 36(Pt 1):120-5

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Abstract


A protein quality control system, consisting of molecular chaperones and proteases, controls the folding status of proteins and mediates the refolding or degradation of misfolded proteins. Ring-forming AAA+ (ATPase associated with various cellular activities) proteins play crucial roles in both processes by co-operating with either peptidases or chaperone systems. Peptidase-associated AAA+ proteins bind substrates and thread them through their axial channel into the attached proteolytic chambers for degradation. In contrast, the AAA+ protein ClpB evolved independently from an interacting peptidase and co-operates with a cognate Hsp70 (heat-shock protein 70) chaperone system to solubilize and refold aggregated proteins. The activity of this bi-chaperone system is crucial for the survival of bacteria, yeast and plants during severe stress conditions. Hsp70 acts at initial stages of the disaggregation process, enabling ClpB to extract single unfolded polypeptides from the aggregate via a threading activity. Although both classes of AAA+ proteins share a common threading activity, it is apparent that their divergent evolution translates into specific mechanisms, reflecting adaptations to their respective functions. The ClpB-specific M-domain (middle domain) represents such an extra feature that verifies ClpB as the central disaggregase in vivo. M-domains act as regulatory devices to control both ClpB ATPase activity and the Hsp70-dependent binding of aggregated proteins to the ClpB pore, thereby coupling the Hsp70 chaperone activity with the ClpB threading motor to ensure efficient protein disaggregation.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't | Review
Authors
Mogk A, Haslberger T, Tessarz P, Bukau B
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