Experimental Milestones in the Discovery of Molecular Chaperones as Polypeptide Unfolding Enzymes.

Details

Ressource 1Download: BIB_3C8C94E55F99.P001.pdf (2733.25 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_FB5D959FE745
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
Experimental Milestones in the Discovery of Molecular Chaperones as Polypeptide Unfolding Enzymes.
Journal
Annual Review of Biochemistry
Author(s)
Finka A., Mattoo R.U., Goloubinoff P.
ISSN
1545-4509 (Electronic)
ISSN-L
0066-4154
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
85
Pages
715-742
Language
english
Abstract
Molecular chaperones control the cellular folding, assembly, unfolding, disassembly, translocation, activation, inactivation, disaggregation, and degradation of proteins. In 1989, groundbreaking experiments demonstrated that a purified chaperone can bind and prevent the aggregation of artificially unfolded polypeptides and use ATP to dissociate and convert them into native proteins. A decade later, other chaperones were shown to use ATP hydrolysis to unfold and solubilize stable protein aggregates, leading to their native refolding. Presently, the main conserved chaperone families Hsp70, Hsp104, Hsp90, Hsp60, and small heat-shock proteins (sHsps) apparently act as unfolding nanomachines capable of converting functional alternatively folded or toxic misfolded polypeptides into harmless protease-degradable or biologically active native proteins. Being unfoldases, the chaperones can proofread three-dimensional protein structures and thus control protein quality in the cell. Understanding the mechanisms of the cellular unfoldases is central to the design of new therapies against aging, degenerative protein conformational diseases, and specific cancers.

Keywords
Adenosine Triphosphate/chemistry, Adenosine Triphosphate/metabolism, Chaperonin 60/chemistry, Chaperonin 60/genetics, Chaperonin 60/metabolism, Escherichia coli/chemistry, Escherichia coli/metabolism, Gene Expression, HSP110 Heat-Shock Proteins/chemistry, HSP110 Heat-Shock Proteins/genetics, HSP110 Heat-Shock Proteins/metabolism, HSP70 Heat-Shock Proteins/chemistry, HSP70 Heat-Shock Proteins/genetics, HSP70 Heat-Shock Proteins/metabolism, Heat-Shock Proteins, Small/chemistry, Heat-Shock Proteins, Small/genetics, Heat-Shock Proteins, Small/metabolism, Humans, Mitochondrial Proteins/chemistry, Mitochondrial Proteins/genetics, Mitochondrial Proteins/metabolism, Models, Molecular, Protein Aggregates, Protein Folding, Protein Structure, Quaternary, Protein Unfolding, Rhodospirillum rubrum/chemistry, Rhodospirillum rubrum/metabolism, Hsp104, Hsp110, Hsp60, Hsp70, heat-shock proteins, protein homeostasis, sHsps, small heat-shock proteins, unfoldases
Pubmed
Web of science
Open Access
Yes
Create date
13/06/2017 17:38
Last modification date
20/08/2019 16:26
Usage data