Refolding of Substrates Bound to Small Hsps Relies on a Disaggregation Reaction Mediated Most Efficiently by ClpB/DnaK

• Published in: The Journal of biological chemistry Vol. 278; no. 33; pp. 31033 - 31042
• Main Authors: Mogk, Axel, Schlieker, Christian, Friedrich, Kenneth L., Schönfeld, Hans-Joachim, Vierling, Elizabeth, Bukau, Bernd
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2003; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Endopeptidase Clp; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Heat-Shock Proteins - chemistry; Heat-Shock Proteins - metabolism; Hot Temperature; HSP70 Heat-Shock Proteins - chemistry; HSP70 Heat-Shock Proteins - metabolism; Malate Dehydrogenase - metabolism; Molecular Chaperones - chemistry; Molecular Chaperones - metabolism; Protein Binding; Protein Denaturation; Protein Folding; Solubility
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M303587200

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.