title: Protein disaggregation mediated by heat-shock protein Hsp104.
abstract: The heat-inducible members of the Hsp100 (or Clp) family of proteins share a common function in helping organisms to survive extreme stress, but the basic mechanism through which these proteins function is not understood. Hsp104 protects cells against a variety of stresses, under many physiological conditions, and its function has been evolutionarily conserved, at least from Saccharomyces cerevisiae to Arabidopsis thaliana. Homology with the Escherichia coli ClpA protein suggests that Hsp104 may provide stress tolerance by helping to rid the cell of heat-denatured proteins through proteolysis. But genetic analysis indicates that Hsp104 may function like Hsp70 as a molecular chaperone. Here we investigate the role of Hsp104 in vivo using a temperature-sensitive Vibrio harveyi luciferase-fusion protein as a test substrate. We find that Hsp104 does not protect luciferase from thermal denaturation, nor does it promote proteolysis of luciferase. Rather, Hsp104 functions in a manner not previously described for other heat-shock proteins: it mediates the resolubilization of heat-inactivated luciferase from insoluble aggregates.
authors.affiliation: Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Illinois 60637.
authors.forename: D A
authors.initials: DA
authors.lastname: Parsell
authors.forename: A S
authors.initials: AS
authors.lastname: Kowal
authors.forename: M A
authors.initials: MA
authors.lastname: Singer
authors.forename: S
authors.initials: S
authors.lastname: Lindquist
mesh_terms: D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology*; D006358:Hot Temperature; D008156:Luciferases / Q000378:metabolism; D018832:Molecular Chaperones / Q000502:physiology*; D009154:Mutation; D011489:Protein Denaturation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012995:Solubility
chemical_list: D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D008156:Luciferases