Solubilization of aggregated proteins by ClpB/DnaK relies on the continuous extraction of unfolded polypeptides.
The AAA+ chaperone ClpB solubilizes in cooperation with the DnaK chaperone system aggregated proteins. The mechanistic features of the protein disaggregation process are poorly understood. Here, we investigated the mechanism of ClpB/DnaK-dependent solubilization of heat-aggregated malate dehydrogenase (MDH) by following characteristics of MDH aggregates during the disaggregation reaction. We demonstrate that disaggregation is achieved by the continuous extraction of unfolded MDH molecules and not by fragmentation of large MDH aggregates. These findings support a ClpB-dependent threading mechanism as an integral part of the disaggregation reaction.
Schlieker
Christian
C
ZMBH, Universität Heidelberg, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany.
Tews
Ivo
I
Bukau
Bernd
B
Mogk
Axel
A
D000251:Adenosine Triphosphatases / Q000378:metabolism; D018834:Chaperonin 60 / Q000378:metabolism; D019281:Dimerization; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008027:Light; D008291:Malate Dehydrogenase / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D012542:Scattering, Radiation; D012995:Solubility; D013696:Temperature; D013997:Time Factors
D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D010455:Peptides; D008291:Malate Dehydrogenase; D000251:Adenosine Triphosphatases