University of Oulu

Moilanen, A., Korhonen, K., Saaranen, M., Ruddock, L. (2018) Molecular analysis of human Ero1 reveals novel regulatory mechanisms for oxidative protein folding. Life Science Alliance, 1 (3), e201800090. doi:10.26508/lsa.201800090

Molecular analysis of human Ero1 reveals novel regulatory mechanisms for oxidative protein folding

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Author: Moilanen, Antti1; Korhonen, Kati1; Saaranen, Mirva J1;
Organizations: 1Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
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Language: English
Published: Life Science Alliance, 2018
Publish Date: 2019-02-20


Oxidative protein folding in the ER is driven mainly by oxidases of the endoplasmic reticulum oxidoreductin 1 (Ero1) family. Their action is regulated to avoid cell stress, including hyperoxidation. Previously published regulatory mechanisms are based on the rearrangement of active site and regulatory disulfides. In this study, we identify two novel regulatory mechanisms. First, both human Ero1 isoforms exist in a dynamic mixed disulfide complex with protein disulfide isomerase, which involves cysteines (Cys166 in Ero1α and Cys165 in Ero1β) that have previously been regarded as being nonfunctional. Second, our kinetic studies reveal that Ero1 not only has a high affinity for molecular oxygen as the terminal acceptor of electrons but also that there is a high cooperativity of binding (Hill coefficient >3). This allows Ero1 to maintain high activity under hypoxic conditions, without compromising cellular viability under hyper-hypoxic conditions. These data, together with novel mechanistic details of differences in activation between the two human Ero1 isoforms, provide important new insights into the catalytic cycle of human Ero1 and how they have been fine-tuned to operate at low oxygen concentrations.

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Series: Life science alliance
ISSN: 2575-1077
ISSN-E: 2575-1077
ISSN-L: 2575-1077
Volume: 1
Issue: 3
Article number: e201800090
DOI: 10.26508/lsa.201800090
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by the Academy of Finland (grants 266457 and 272573), Sigrid Juselius Foundation, The Finnish Cultural Foundation, and Biocenter Oulu.
Academy of Finland Grant Number: 272573
Detailed Information: 272573 (Academy of Finland Funding decision)
Copyright information: © 2018 Moilanen et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at