Size-dependent disaggregation of stable protein aggregates by the DnaK chaperone machinery.

Détails

ID Serval
serval:BIB_F41C7C4EC98C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Size-dependent disaggregation of stable protein aggregates by the DnaK chaperone machinery.
Périodique
Journal of Biological Chemistry
Auteur(s)
Diamant S., Ben-Zvi A.P., Bukau B., Goloubinoff P.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
275
Numéro
28
Pages
21107-21113
Langue
anglais
Résumé
Classic in vitro studies show that the Hsp70 chaperone system from Escherichia coli (DnaK-DnaJ-GrpE, the DnaK system) can bind to proteins, prevent aggregation, and promote the correct refolding of chaperone-bound polypeptides into native proteins. However, little is known about how the DnaK system handles proteins that have already aggregated. In this study, glucose-6-phosphate dehydrogenase was used as a model system to generate stable populations of protein aggregates comprising controlled ranges of particle sizes. The DnaK system recognized the glucose-6-phosphate dehydrogenase aggregates as authentic substrates and specifically solubilized and refolded the protein into a native enzyme. The efficiency of disaggregation by the DnaK system was high with small aggregates, but the efficiency decreased as the size of the aggregates increased. High folding efficiency was restored by either excess DnaK or substoichiometric amounts of the chaperone ClpB. We suggest a mechanism whereby the DnaK system can readily solubilize small aggregates and refold them into active proteins. With large aggregates, however, the binding sites for the DnaK system had to be dynamically exposed with excess DnaK or the catalytic action of ClpB and ATP. Disaggregation by the DnaK machinery in the cell can solubilize early aggregates that formed accidentally during chaperone-assisted protein folding or that escaped the protection of "holding" chaperones during stress.
Mots-clé
Chromatography, Gel, Escherichia coli/metabolism, Escherichia coli Proteins, Glucosephosphate Dehydrogenase/chemistry, Glucosephosphate Dehydrogenase/metabolism, HSP70 Heat-Shock Proteins/metabolism, Kinetics, Leuconostoc/enzymology, Molecular Chaperones/metabolism, Protein Denaturation, Protein Folding
Pubmed
Web of science
Création de la notice
24/01/2008 21:02
Dernière modification de la notice
03/03/2018 22:43
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