Dicarboxylic amino acids and glycine-betaine regulate chaperone-mediated protein-disaggregation under stress.
Diamant, Sophia 1; Rosenthal, David 1; Azem, Abdussalam 2; Eliahu, Noa 1; Ben-Zvi, Anat Peres 1; Goloubinoff, Pierre 1,3,*
[Article] Molecular Microbiology. 49(2):401-410, July 2003.

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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.

(C) 2003 Blackwell Science Ltd.