Mechanisms of active solubilization of stable protein aggregates by molecular chaperones

Details

Serval ID
serval:BIB_A6E0423C3542
Type
A part of a book
Collection
Publications
Title
Mechanisms of active solubilization of stable protein aggregates by molecular chaperones
Title of the book
Protein Misfolding, Aggregation, and Conformational Diseases. Part A.
Author(s)
Goloubinoff P., Ben-Zvi A.P.
Publisher
Springer
Address of publication
New York
ISBN
978-0-387-25918-5
Publication state
Published
Issued date
2006
Editor
Uversky V.N., Fink A.L.
Volume
4
Series
Protein Reviews
Chapter
8
Pages
165-174
Language
english
Notes
Part A: Protein Aggregation and Conformational Diseases
Abstract
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.
Create date
14/04/2014 10:12
Last modification date
20/08/2019 16:11
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