Bacterial suppressor-of-copper-sensitivity proteins exhibit diverse thiol-disulfide oxidoreductase cellular functions

Summary: Disulfide bond (Dsb) oxidoreductases involved in oxidative protein folding govern bacterial survival and virulence. Over the past decade, oligomerization has emerged as a potential factor that dictates oxidoreductase activities. To investigate the role of oligomerization, we studied three D...

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Main Authors: Yaoqin Hong, Jilong Qin, Lachlan Mitchell, Jason J. Paxman, Begoña Heras, Makrina Totsika
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224026178
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author Yaoqin Hong
Jilong Qin
Lachlan Mitchell
Jason J. Paxman
Begoña Heras
Makrina Totsika
author_facet Yaoqin Hong
Jilong Qin
Lachlan Mitchell
Jason J. Paxman
Begoña Heras
Makrina Totsika
author_sort Yaoqin Hong
collection DOAJ
description Summary: Disulfide bond (Dsb) oxidoreductases involved in oxidative protein folding govern bacterial survival and virulence. Over the past decade, oligomerization has emerged as a potential factor that dictates oxidoreductase activities. To investigate the role of oligomerization, we studied three Dsb-like ScsC oxidoreductases involved in copper resistance: the monomeric Salmonella enterica StScsC, and the trimeric Proteus mirabilis PmScsC and Caulobacter crescentus CcScsC. For copper sequestration, ScsC proteins must remain in the reduced form. However, all three ScsC proteins exhibit both dithiol oxidation and disulfide reduction activity, despite structural differences and previously reported limited in vitro activity. Most ScsC reductase activity relies on interactions with E. coli DsbD reductase, while oxidase activity depends on environmental oxidation. Interestingly, engineered monomeric PmScsC interacts effectively with the E. coli DsbB oxidase, at the partial expense of its reductase activity. These findings highlight oligomerization of oxidoreductases as a steric hindrance strategy to block undesirable upstream oxidative interactions.
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issn 2589-0042
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publisher Elsevier
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spelling doaj-art-2aa71124dfb94099b7fff4e84f62ec082025-08-20T01:59:39ZengElsevieriScience2589-00422024-12-01271211139210.1016/j.isci.2024.111392Bacterial suppressor-of-copper-sensitivity proteins exhibit diverse thiol-disulfide oxidoreductase cellular functionsYaoqin Hong0Jilong Qin1Lachlan Mitchell2Jason J. Paxman3Begoña Heras4Makrina Totsika5Centre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia; Corresponding authorCentre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaCentre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia; Corresponding authorSummary: Disulfide bond (Dsb) oxidoreductases involved in oxidative protein folding govern bacterial survival and virulence. Over the past decade, oligomerization has emerged as a potential factor that dictates oxidoreductase activities. To investigate the role of oligomerization, we studied three Dsb-like ScsC oxidoreductases involved in copper resistance: the monomeric Salmonella enterica StScsC, and the trimeric Proteus mirabilis PmScsC and Caulobacter crescentus CcScsC. For copper sequestration, ScsC proteins must remain in the reduced form. However, all three ScsC proteins exhibit both dithiol oxidation and disulfide reduction activity, despite structural differences and previously reported limited in vitro activity. Most ScsC reductase activity relies on interactions with E. coli DsbD reductase, while oxidase activity depends on environmental oxidation. Interestingly, engineered monomeric PmScsC interacts effectively with the E. coli DsbB oxidase, at the partial expense of its reductase activity. These findings highlight oligomerization of oxidoreductases as a steric hindrance strategy to block undesirable upstream oxidative interactions.http://www.sciencedirect.com/science/article/pii/S2589004224026178BiochemistryMicrobiologyStructural biology
spellingShingle Yaoqin Hong
Jilong Qin
Lachlan Mitchell
Jason J. Paxman
Begoña Heras
Makrina Totsika
Bacterial suppressor-of-copper-sensitivity proteins exhibit diverse thiol-disulfide oxidoreductase cellular functions
iScience
Biochemistry
Microbiology
Structural biology
title Bacterial suppressor-of-copper-sensitivity proteins exhibit diverse thiol-disulfide oxidoreductase cellular functions
title_full Bacterial suppressor-of-copper-sensitivity proteins exhibit diverse thiol-disulfide oxidoreductase cellular functions
title_fullStr Bacterial suppressor-of-copper-sensitivity proteins exhibit diverse thiol-disulfide oxidoreductase cellular functions
title_full_unstemmed Bacterial suppressor-of-copper-sensitivity proteins exhibit diverse thiol-disulfide oxidoreductase cellular functions
title_short Bacterial suppressor-of-copper-sensitivity proteins exhibit diverse thiol-disulfide oxidoreductase cellular functions
title_sort bacterial suppressor of copper sensitivity proteins exhibit diverse thiol disulfide oxidoreductase cellular functions
topic Biochemistry
Microbiology
Structural biology
url http://www.sciencedirect.com/science/article/pii/S2589004224026178
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