Dicarboxylic amino acids and glycine-betaine regulate chaperone-mediated protein-disaggregation under stress.
Active protein-disaggregation by a chaperone network composed of ClpB and DnaK + DnaJ + GrpE is essential for the recovery of stress-induced protein aggregates in vitro and in Escherichia coli cells. K-glutamate and glycine-betaine (betaine) naturally accumulate in salt-stressed cells. In addition to providing thermo-protection to native proteins, we found that these osmolytes can strongly and specifically activate ClpB, resulting in an increased efficiency of chaperone-mediated protein disaggregation. Moreover, factors that inhibited the chaperone network by impairing the stability of the ClpB oligomer, such as natural polyamines, dilution, or high salt, were efficiently counteracted by K-glutamate or betaine. The combined protective, counter-negative and net activatory effects of K-glutamate and betaine, allowed protein disaggregation and refolding under heat-shock temperatures that otherwise cause protein aggregation in vitro and in the cell. Mesophilic organisms may thus benefit from a thermotolerant osmolyte-activated chaperone mechanism that can actively rescue protein aggregates, correctly refold and maintain them in a native state under heat-shock conditions.
Diamant
Sophia
S
Department of Plant Sciences, Institute of Life Science, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
Rosenthal
David
D
Azem
Abdussalam
A
Eliahu
Noa
N
Ben-Zvi
Anat Peres
AP
Goloubinoff
Pierre
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000600:Amino Acids, Dicarboxylic / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D001622:Betaine / Q000378:metabolism*; D049071:Endopeptidase Clp; D004926:Escherichia coli / Q000166:cytology / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D011489:Protein Denaturation; D017510:Protein Folding; D012492:Salts / Q000378:metabolism
D000600:Amino Acids, Dicarboxylic; D001426:Bacterial Proteins; C494635:DnaJ protein, E coli; D029968:Escherichia coli Proteins; C068113:GrpE protein, Bacteria; C489400:GrpE protein, E coli; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012492:Salts; D001622:Betaine; D000255:Adenosine Triphosphate; D008291:Malate Dehydrogenase; D049071:Endopeptidase Clp; C063842:dnaK protein, E coli; C069775:ClpB protein, E coli; D005998:Glycine