Active solubilization and refolding of stable protein aggregates by cooperative unfolding action of individual hsp70 chaperones.

Details

Serval ID
serval:BIB_85CE7270F7F4
Type
Article: article from journal or magazin.
Collection
Publications
Title
Active solubilization and refolding of stable protein aggregates by cooperative unfolding action of individual hsp70 chaperones.
Journal
Journal of Biological Chemistry
Author(s)
Ben-Zvi A., De Los Rios P., Dietler G., Goloubinoff P.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
279
Number
36
Pages
37298-37303
Language
english
Abstract
Hsp70 is a central molecular chaperone that passively prevents protein aggregation and uses the energy of ATP hydrolysis to solubilize, translocate, and mediate the proper refolding of proteins in the cell. Yet, the molecular mechanism by which the active Hsp70 chaperone functions are achieved remains unclear. Here, we show that the bacterial Hsp70 (DnaK) can actively unfold misfolded structures in aggregated polypeptides, leading to gradual disaggregation. We found that the specific unfolding and disaggregation activities of individual DnaK molecules were optimal for large aggregates but dramatically decreased for small aggregates. The active unfolding of the smallest aggregates, leading to proper global refolding, required the cooperative action of several DnaK molecules per misfolded polypeptide. This finding suggests that the unique ATP-fueled locking/unlocking mechanism of the Hsp70 chaperones can recruit random chaperone motions to locally unfold misfolded structures and gradually disentangle stable aggregates into refoldable proteins.
Keywords
Chromatography, Gel, Escherichia coli Proteins/metabolism, HSP70 Heat-Shock Proteins/metabolism, Leuconostoc/metabolism, Protein Binding, Protein Folding, Solubility
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 21:02
Last modification date
20/08/2019 15:45
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