Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network.

Details

Serval ID
serval:BIB_6C7982C5386E
Type
Article: article from journal or magazin.
Collection
Publications
Title
Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Goloubinoff P., Mogk A., Ben-Zvi A.P., Tomoyasu T., Bukau B.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Publication state
Published
Issued date
1999
Volume
96
Number
24
Pages
13732-13737
Language
english
Abstract
A major activity of molecular chaperones is to prevent aggregation and refold misfolded proteins. However, when allowed to form, protein aggregates are refolded poorly by most chaperones. We show here that the sequential action of two Escherichia coli chaperone systems, ClpB and DnaK-DnaJ-GrpE, can efficiently solubilize excess amounts of protein aggregates and refold them into active proteins. Measurements of aggregate turbidity, Congo red, and 4,4'-dianilino-1, 1'-binaphthyl-5,5'-disulfonic acid binding, and of the disaggregation/refolding kinetics by using a specific ClpB inhibitor, suggest a mechanism where (i) ClpB directly binds protein aggregates, ATP induces structural changes in ClpB, which (ii) increase hydrophobic exposure of the aggregates and (iii) allow DnaK-DnaJ-GrpE to bind and mediate dissociation and refolding of solubilized polypeptides into native proteins. This efficient mechanism, whereby chaperones can catalytically solubilize and refold a wide variety of large and stable protein aggregates, is a major addition to the molecular arsenal of the cell to cope with protein damage induced by stress or pathological states.
Keywords
Bacterial Proteins/metabolism, Escherichia coli Proteins, HSP40 Heat-Shock Proteins, HSP70 Heat-Shock Proteins/metabolism, Heat-Shock Proteins/metabolism, Heating, Malate Dehydrogenase/metabolism, Molecular Chaperones/metabolism, Protein Denaturation, Protein Folding, Solubility, Substrate Specificity
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 21:02
Last modification date
20/08/2019 15:26
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