The AAA+ chaperone ClpB mediates the reactivation of aggregated proteins in cooperation with the DnaK chaperone system. ClpB consists of two AAA domains that drive the ATP-dependent threading of substrates through a central translocation channel. Its unique middle (M) domain forms a coiled-coil structure that laterally protrudes from the ClpB ring and is essential for aggregate solubilization. Here, we demonstrate that the conserved helix 3 of the M domain is specifically required for the DnaK-dependent shuffling of aggregated proteins, but not of soluble denatured substrates, to the pore entrance of the ClpB translocation channel. Helix 3 exhibits nucleotide-driven conformational changes possibly involving a transition between folded and unfolded states. This molecular switch controls the ClpB ATPase cycle by contacting the first ATPase domain and establishes the M domain as a regulatory device that acts in the disaggregation process by coupling the threading motor of ClpB with the DnaK chaperone activity. © 2007 Elsevier Inc. All rights reserved.
CITATION STYLE
Haslberger, T., Weibezahn, J., Zahn, R., Lee, S., Tsai, F. T. F., Bukau, B., & Mogk, A. (2007). M Domains Couple the ClpB Threading Motor with the DnaK Chaperone Activity. Molecular Cell, 25(2), 247–260. https://doi.org/10.1016/j.molcel.2006.11.008
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