A temperature-dependent switch from chaperone to protease in a widely conserved heat shock protein

Misfolding or unfolding of polypeptides can occur as a consequence of envir onmental stress and spontaneous mutation. The abundance of general chaperon es and proteases suggests that cells distinguish between proteins that can be refolded and "hopeless" cases fated to enter the proteolytic pathway. Th e mechanisms controlling this key metabolic decision are not well understoo d. We show here that the widely conserved heat shock protein DegP (HtrA) ha s both general molecular chaperone and proteolytic activities. The chaperon e function dominates at low temperatures, while the proteolytic activity is present at elevated temperatures. These results show that a single cellula r factor can switch between two key pathways, controlling protein stability and turnover. Implications of this finding for intracellular protein metab olism are discussed.