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

Tobias Haslberger; Jimena Weibezahn; Regina Zahn; Sukyeong Lee; Francis T F Tsai; Bernd Bukau; Axel Mogk

doi:10.1016/j.molcel.2006.11.008

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.

Authors

Tobias Haslberger¹, Jimena Weibezahn, Regina Zahn, Sukyeong Lee, Francis T F Tsai, Bernd Bukau, Axel Mogk

Affiliation

¹ ZMBH, Universität Heidelberg, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany.

PMID: 17244532
DOI: 10.1016/j.molcel.2006.11.008

Abstract

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

Substances

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