ERdj5 is the ER reductase that catalyzes the removal of non-native disulfides and correct folding of the LDL receptor

Oka, O. B. V. , Pringle, M. A. , Schopp, I. M., Braakman, I. and Bulleid, N. J. (2013) ERdj5 is the ER reductase that catalyzes the removal of non-native disulfides and correct folding of the LDL receptor. Molecular Cell, 50(6), pp. 793-804. (doi: 10.1016/j.molcel.2013.05.014)

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ERdj5 is a member of the protein disulfide isomerase family of proteins localized to the endoplasmic reticulum (ER) of mammalian cells. To date, only a limited number of substrates for ERdj5 are known. Here we identify a number of endogenous substrates that form mixed disulfides with ERdj5, greatly expanding its client repertoire. ERdj5 previously had been thought to exclusively reduce disulfides in proteins destined for dislocation to the cytosol for degradation. However, we demonstrate here that for one of the identified substrates, the low-density lipoprotein receptor (LDLR), ERdj5 is required not for degradation, but rather for efficient folding. Our results demonstrate that the crucial role of ERdj5 is to reduce non-native disulfides formed during productive folding and that this requirement is dependent on its interaction with BiP. Hence, ERdj5 acts as the ER reductase, both preparing misfolded proteins for degradation and catalyzing the folding of proteins that form obligatory non-native disulfides.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Bulleid, Professor Neil and Schopp, Miss Isabel and Pringle, Mrs Marie and Oka, Dr Ojore
Authors: Oka, O. B. V., Pringle, M. A., Schopp, I. M., Braakman, I., and Bulleid, N. J.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Molecular Cell
ISSN (Online):1097-4164
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Molecular Cell 50(6):793-804
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