1. Refolding of substrates bound to small Hsps relies on a disaggregation reaction mediated most efficiently by ClpB/DnaK
- Author
-
Bernd Bukau, Hans-Joachim Schönfeld, Kenneth L. Friedrich, Elizabeth Vierling, Axel Mogk, and Christian Schlieker
- Subjects
Protein Denaturation ,Protein Folding ,Hot Temperature ,Endopeptidase Clp ,genetic processes ,Plasma protein binding ,Biology ,Biochemistry ,Cellular protein ,Malate Dehydrogenase ,Animals ,HSP70 Heat-Shock Proteins ,Molecular Biology ,Small Heat-Shock Proteins ,Heat-Shock Proteins ,Escherichia coli Proteins ,Cell Biology ,In vitro ,Heat stress ,Solubility ,biological sciences ,bacteria ,Protein folding ,CLPB ,Molecular Chaperones ,Protein Binding - Abstract
Small heat shock proteins (sHsps) are ubiquitous molecular chaperones that bind denatured proteins in vitro, thereby facilitating their subsequent refolding by ATP-dependent chaperones. The mechanistic basis of this refolding process is poorly defined. We demonstrate that substrates complexed to sHsps from various sources are not released spontaneously. Dissociation and refolding of sHsp bound substrates relies on a disaggregation reaction mediated by the DnaK system, or, more efficiently, by ClpB/DnaK. While the DnaK system alone works for small, soluble sHsp/substrate complexes, ClpB/DnaK-mediated protein refolding is fastest for large, insoluble protein aggregates with incorporated sHsps. Such conditions reflect the situation in vivo, where sHsps are usually associated with insoluble proteins during heat stress. We therefore propose that sHsp function in cellular protein quality control is to promote rapid resolubilization of aggregated proteins, formed upon severe heat stress, by DnaK or ClpB/DnaK.
- Published
- 2003