Review: mechanisms of disaggregation and refolding of stable protein aggregates by molecular chaperones.

Détails

ID Serval
serval:BIB_A96A0172D471
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Review: mechanisms of disaggregation and refolding of stable protein aggregates by molecular chaperones.
Périodique
Journal of Structural Biology
Auteur(s)
Ben-Zvi A.P., Goloubinoff P.
ISSN
1047-8477 (Print)
ISSN-L
1047-8477
Statut éditorial
Publié
Date de publication
2001
Volume
135
Numéro
2
Pages
84-93
Langue
anglais
Résumé
Molecular chaperones are essential for the correct folding of proteins in the cell under physiological and stress conditions. Two activities have been traditionally attributed to molecular chaperones: (1) preventing aggregation of unfolded polypeptides and (2) assisting in the correct refolding of chaperone-bound denatured polypeptides. We discuss here a novel function of molecular chaperones: catalytic solubilization and refolding of stable protein aggregates. In Escherichia coli, disaggregation is carried out by a network of ATPase chaperones consisting of a DnaK core, assisted by the cochaperones DnaJ, GrpE, ClpB, and GroEL-GroES. We suggest a sequential mechanism in which (a) ClpB exposes new DnaK-binding sites on the surface of the stable protein aggregates; (b) DnaK binds the aggregate surfaces and, by doing so, melts the incorrect hydrophobic associations between aggregated polypeptides; (c) ATP hydrolysis and DnaK release allow local intramolecular refolding of native domains, leading to a gradual weakening of improper intermolecular links; (d) DnaK and GroEL complete refolding of solubilized polypeptide chains into native proteins. Thus, active disaggregation by the chaperone network can serve as a central cellular tool for the recovery of native proteins from stress-induced aggregates and actively remove disease-causing toxic aggregates, such as polyglutamine-rich proteins, amyloid plaques, and prions.
Mots-clé
Adenosine Triphosphatases/pharmacology, Adenosine Triphosphatases/physiology, Animals, Humans, Macromolecular Substances, Molecular Chaperones/pharmacology, Molecular Chaperones/physiology, Protein Folding, Protein Renaturation/drug effects
Pubmed
Web of science
Création de la notice
24/01/2008 21:02
Dernière modification de la notice
20/08/2019 16:13
Données d'usage