Molecular chaperones as enzymes that catalytically unfold misfolded polypeptides.

Details

Serval ID
serval:BIB_C3D18AC6F90A
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
Molecular chaperones as enzymes that catalytically unfold misfolded polypeptides.
Journal
FEBS Letters
Author(s)
Priya S., Sharma S.K., Goloubinoff P.
ISSN
1873-3468 (Electronic)
ISSN-L
0014-5793
Publication state
Published
Issued date
2013
Volume
587
Number
13
Pages
1981-1987
Language
english
Abstract
Stress-denatured or de novo synthesized and translocated unfolded polypeptides can spontaneously reach their native state without assistance of other proteins. Yet, the pathway to native folding is complex, stress-sensitive and prone to errors. Toxic misfolded and aggregated conformers may accumulate in cells and lead to degenerative diseases. Members of the canonical conserved families of molecular chaperones, Hsp100s, Hsp70/110/40s, Hsp60/CCTs, the small Hsps and probably also Hsp90s, can recognize and bind with high affinity, abnormally exposed hydrophobic surfaces on misfolded and aggregated polypeptides. Binding to Hsp100, Hsp70, Hsp110, Hsp40, Hsp60, CCTs and Trigger factor may cause partial unfolding of the misfolded polypeptide substrates, and ATP hydrolysis can induce further unfolding and release from the chaperone, leading to spontaneous refolding into native proteins with low-affinity for the chaperones. Hence, specific chaperones act as catalytic polypeptide unfolding isomerases, rerouting cytotoxic misfolded and aggregated polypeptides back onto their physiological native refolding pathway, thus averting the onset of protein conformational diseases.
Keywords
Animals, Biocatalysis, Chaperonins/physiology, Heat-Shock Proteins/physiology, Humans, Peptides/metabolism, Protein Unfolding, Proteostasis Deficiencies/enzymology
Pubmed
Web of science
Open Access
Yes
Create date
21/05/2013 14:14
Last modification date
20/08/2019 16:39
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