MULTIPLE EFFECTS OF TREHALOSE ON PROTEIN-FOLDING IN-VITRO AND IN-VIVO

The disaccharide trehalose is produced in large quantities by diverse organisms during a variety of stresses. Trehalose prevents proteins fr om denaturing at high temperatures in vitro, but its function in stres s tolerance in vivo is controversial. We report that trehalose stabili zes proteins in yeast cells during heat shock. Surprisingly, trehalose also suppresses the aggregation of denatured proteins, maintaining th em in a partially-folded state from which they can be reactivated by m olecular chaperones. The continued presence of trehalose, however, int erferes with refolding, suggesting why it is rapidly hydrolyzed follow ing heat shock. These findings reconcile conflicting reports on the ro le of trehalose in stress tolerance, provide a novel tool for accessin g protein folding intermediates, and define new parameters for modulat ing stress tolerance and protein aggregation.