Thiol-disulfide exchange between the PDI family of oxidoreductases negates the requirement for an oxidase or reductase for each enzyme

Oka, O. , Yeoh, H. and Bulleid, N. (2015) Thiol-disulfide exchange between the PDI family of oxidoreductases negates the requirement for an oxidase or reductase for each enzyme. Biochemical Journal, 469(2), pp. 279-288. (doi: 10.1042/BJ20141423) (PMID:25989104) (PMCID:PMC4613490))

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The formation of disulfides in proteins entering the secretory pathway is catalysed by the protein disulfide isomerase family of enzymes. These enzymes catalyse the introduction, reduction and isomerisation of disulfides. To function continuously they require an oxidase to reform the disulfide at their active site. To determine how each family member can be recycled to catalyse disulfide exchange, we have studied whether disulfides are transferred between individual PDI family members. We studied disulfide exchange either between purified proteins or by identifying mixed disulfide formation within cells grown in culture. We show that disulfide exchange occurs efficiently and reversibly between specific PDIs. These results have allowed us to define a hierarchy for members of the PDI family, in terms of ability to act as electron acceptors or donors during thiol-disulfide exchange reactions and indicate that there is no kinetic barrier to the exchange of disulfides between several PDI proteins. Such promiscuous disulfide exchange negates the necessity for each enzyme to be oxidised by Ero1 or reduced by a reductive system. The lack of kinetic separation of the oxidative and reductive pathways in mammalian cells contrasts sharply with the equivalent systems for native disulfide formation within the bacterial periplasm.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Bulleid, Professor Neil and Oka, Dr Ojore
Authors: Oka, O., Yeoh, H., and Bulleid, N.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Biochemical Journal
Publisher:Portland Press Ltd.
ISSN (Online):1470-8728
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Biochemical Journal 469(2):279-288
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
528621Regulating the redox conditions within the mammalian endoplasmic reticulumNeil BulleidWellcome Trust (WELLCOME)088053/Z/08/ARI MOLECULAR CELL & SYSTEMS BIOLOGY