Mechanisms of active solubilization of stable protein aggregates by molecular chaperones

Détails

ID Serval
serval:BIB_A6E0423C3542
Type
Partie de livre
Collection
Publications
Titre
Mechanisms of active solubilization of stable protein aggregates by molecular chaperones
Titre du livre
Protein Misfolding, Aggregation, and Conformational Diseases. Part A.
Auteur(s)
Goloubinoff P., Ben-Zvi A.P.
Editeur
Springer
Lieu d'édition
New York
ISBN
978-0-387-25918-5
Statut éditorial
Publié
Date de publication
2006
Editeur scientifique
Uversky V.N., Fink A.L.
Volume
4
Série
Protein Reviews
Numéro de chapitre
8
Pages
165-174
Langue
anglais
Notes
Part A: Protein Aggregation and Conformational Diseases
Résumé
Protein destabilization by mutations or external stresses may lead to misfolding and aggregation in the cell. Often, damage is not limited to a simple loss of function, but the hydrophobic exposure of aggregate surfaces may impair membrane functions and promote the aggregation of other proteins. Such a "proteinacious infectious" behavior is not limited to prion diseases. It is associated to most protein-misfolding neurodegenerative diseases and to aging in general. With the molecular chaperones and proteases, cells have evolved powerful tools that can specifically recognize and act upon misfolded and aggregated proteins. Whereas some chaperones passively prevent aggregate formation and propagation, others actively unfold and solubilize stable aggregates. In particular, ATPase chaperones and proteases serve as an intracellular defense network that can specifically identify and actively remove by refolding or degradation potentially infectious cytotoxic aggregates. Here we discuss two types of molecular mechanisms by which ATPase chaperones may actively solubilize stable aggregates: (1) unfolding by power strokes, using the Hsp100 ring chaperones, and (2) unfolding by random movements of individual Hsp70 molecules. In bacteria, fungi, and plants, the two mechanisms are key for reducing protein damages from abiotic stresses. In animals devoid of Hsp100, Hsp70 appears as the core element of the chaperone network, preventing the formation and actively removing disease-causing protein aggregates.
Création de la notice
14/04/2014 10:12
Dernière modification de la notice
20/08/2019 16:11
Données d'usage