PROTEIN DISAGGREGATION MEDIATED BY HEAT-SHOCK PROTEIN HSP104

THE heat-inducible members of the Hsp100 (or Clp) family of proteins s hare a common function in helping organisms to survive extreme stress, but the basic mechanism through which these proteins function is not understood(1-5) Hsp104 protects cells against a variety of stresses, u nder many physiological conditions(6,7) and its function has been evol utionarily conserved, at least from Saccharomyces cerevisiae to Arabid opsis thaliana(25). Homology with the Escherichia coli ClpA protein su ggests that Hsp104 may provide stress tolerance by helping to rid the tell of heat-denatured proteins through proteolysis(1). But genetic an alysis indicates that Hsp104 may function like Hsp70 as a molecular ch aperones(8). Here we investigate the role of Hsp104 in vivo using a te mperature-sensitive Vibrio harveyi luciferase-fusion protein as a test substrate(9). We find that Hsp104 does not protect luciferase from th ermal denaturation, nor does it promote proteolysis of luciferase. Rat her, Hsp104 functions in a manner not previously described for other h eat-shock proteins: it mediates the resolubilization of heat-inactivat ed luciferase from insoluble aggregates.