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The redox switch that regulates molecular chaperones

Conway, Myra E.; Lee, Christopher

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Myra Conway
Occasional Associate Lecturer - CHSS - DAS

Christopher Lee


© 2015 by De Gruyter. Modification of reactive cysteine residues plays an integral role in redox-regulated reactions. Oxidation of thiolate anions to sulphenic acid can result in disulphide bond formation, or overoxidation to sulphonic acid, representing reversible and irreversible endpoints of cysteine oxidation, respectively. The antioxidant systems of the cell, including the thioredoxin and glutaredoxin systems, aim to prevent these higher and irreversible oxidation states. This is important as these redox transitions have numerous roles in regulating the structure/function relationship of proteins. Proteins with redox-active switches as described for peroxiredoxin (Prx) and protein disulphide isomerase (PDI) can undergo dynamic structural rearrangement resulting in a gain of function. For Prx, transition from cysteine sulphenic acid to sulphinic acid is described as an adaptive response during increased cellular stress causing Prx to form higher molecular weight aggregates, switching its role from antioxidant to molecular chaperone. Evidence in support of PDI as a redox-regulated chaperone is also gaining impetus, where oxidation of the redox-active CXXC regions causes a structural change, exposing its hydrophobic region, facilitating polypeptide folding. In this review, we will focus on these two chaperones that are directly regulated through thiol-disulphide exchange and detail how these redox-induced switches allow for dual activity. Moreover, we will introduce a new role for a metabolic protein, the branched-chain aminotransferase, and discuss how it shares common mechanistic features with these well-documented chaperones. Together, the physiological importance of the redox regulation of these proteins under pathological conditions such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis will be discussed to illustrate the impact and importance of correct folding and chaperone-mediated activity.


Conway, M. E., & Lee, C. (2015). The redox switch that regulates molecular chaperones. BioMolecular Concepts, 6(4), 269-284.

Journal Article Type Review
Acceptance Date May 18, 2015
Publication Date Jan 1, 2015
Deposit Date Dec 2, 2015
Publicly Available Date Aug 1, 2016
Journal Biomolecular Concepts
Print ISSN 1868-5021
Electronic ISSN 1868-503X
Publisher De Gruyter
Peer Reviewed Peer Reviewed
Volume 6
Issue 4
Pages 269-284
Keywords CXXC motifs, human branched-chain aminotransferase
protein, molecular chaperones, neurodegeneration,
peroxiredoxins, protein disulphide isomerase,
protein folding, S-nitrosylation
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