M domains couple the ClpB threading motor with the DnaK chaperone activity

Mol Cell. 2007 Jan 26;25(2):247-60. doi: 10.1016/j.molcel.2006.11.008.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Endopeptidase Clp
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / chemistry*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Models, Molecular
  • Molecular Chaperones / metabolism
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Thermus thermophilus / genetics
  • Thermus thermophilus / metabolism


  • Bacterial Proteins
  • Escherichia coli Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Molecular Motor Proteins
  • Adenosine Triphosphate
  • Endopeptidase Clp
  • Adenosine Triphosphatases
  • dnaK protein, E coli
  • ClpB protein, E coli