A molecular chaperone, ClpA, functions like DnaK and DnaJ.
The two major molecular chaperone families that mediate ATP-dependent protein folding and refolding are the heat shock proteins Hsp60s (GroEL) and Hsp70s (DnaK). Clp proteins, like chaperones, are highly conserved, present in all organisms, and contain ATP and polypeptide binding sites. We discovered that ClpA, the ATPase component of the ATP-dependent ClpAP protease, is a molecular chaperone. ClpA performs the ATP-dependent chaperone function of DnaK and DnaJ in the in vitro activation of the plasmid P1 RepA replication initiator protein. RepA is activated by the conversion of dimers to monomers. We show that ClpA targets RepA for degradation by ClpP, demonstrating a direct link between the protein unfolding function of chaperones and proteolysis. In another chaperone assay, ClpA protects luciferase from irreversible heat inactivation but is unable to reactivate luciferase.
Wickner
S
S
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Gottesman
S
S
Skowyra
D
D
Hoskins
J
J
McKenney
K
K
Maurizi
M R
MR
D000251:Adenosine Triphosphatases / Q000302:isolation & purification / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002417:Cattle; D002850:Chromatography, Gel; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D049071:Endopeptidase Clp; D004789:Enzyme Activation; D029968:Escherichia coli Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008970:Molecular Weight; D011506:Proteins; D012697:Serine Endopeptidases / Q000378:metabolism*; D015534:Trans-Activators
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C494635:DnaJ protein, E coli; D029968:Escherichia coli Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D011506:Proteins; D015534:Trans-Activators; C045264:replication initiator protein; D000255:Adenosine Triphosphate; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases; C063842:dnaK protein, E coli; D004265:DNA Helicases