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Dicarboxylic amino acids and glycine‐betaine regulate chaperone‐mediated protein‐disaggregation under stress
Author(s) -
Diamant Sophia,
Rosenthal David,
Azem Abdussalam,
Eliahu Noa,
BenZvi Anat Peres,
Goloubinoff Pierre
Publication year - 2003
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2003.03553.x
Subject(s) - osmolyte , betaine , clpb , biology , chaperone (clinical) , biochemistry , sarcosine , protein aggregation , amino acid , heat shock protein , proteostasis , protein folding , osmoprotectant , microbiology and biotechnology , glycine , biophysics , proline , medicine , pathology , gene
Summary 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.