Protein disaggregation mediated by heat-shock protein Hspl04

DA Parsell, AS Kowal, MA Singer, S Lindquist - Nature, 1994 - nature.com
DA Parsell, AS Kowal, MA Singer, S Lindquist
Nature, 1994nature.com
THE heat-inducible members of the HsplOO (or Clp) family of proteins share a common
function in helping organisms to survive extreme stress, but the basic mechanism through
which these pro-teins function is not understood1–5. Hspl04 protects cells against a variety
of stresses, under many physiological conditions6, 7, and its function has been
evolutionarily conserved, at least from Saccharomyces cerevisiae to Arabidopsis thaliana
25. Homology with the Escherichia coli Clp A protein suggests that Hspl04 may provide …
Abstract
THE heat-inducible members of the HsplOO (or Clp) family of proteins share a common function in helping organisms to survive extreme stress, but the basic mechanism through which these pro-teins function is not understood1–5. Hspl04 protects cells against a variety of stresses, under many physiological conditions6,7, and its function has been evolutionarily conserved, at least from Saccharomyces cerevisiae to Arabidopsis thaliana25. Homology with the Escherichia coli Clp A protein suggests that Hspl04 may provide stress tolerance by helping to rid the cell of heat-denatured proteins through proteolysis1. But genetic analysis indicates that Hspl04 may function like Hsp70 as a molecular chaperone8. Here we investigate the role of Hspl04 in vivo using a temperature-sensitiveVibrio harveyi luciferase-fusion protein as a test substrate9. We find that Hspl04 does not protect luciferase from thermal denaturation, nor does it promote proteolysis of luciferase. Rather, Hspl04 functions in a manner not previously described for other heat-shock proteins: it mediates the resolubilization of heat-inactivated luciferase from insoluble aggregates.
nature.com