Cited by 53Bacterial Genetics and BiotechnologyRedox biology and oxidative stressHeat shock proteins research

The σ R regulon of Streptomyces coelicolor A3(2) reveals a key role in protein quality control during disulphide stress

Kallifidas, Dimitris, Thomas, Derek, Doughty, Phillip, Paget, Mark S. B.·2010·Microbiology

Abstract

Diamide is an artificial disulphide-generating electrophile that mimics an oxidative shift in the cellular thiol–disulphide redox state (disulphide stress). The Gram-positive bacterium Streptomyces coelicolor senses and responds to disulphide stress through the σR–RsrA system, which comprises an extracytoplasmic function (ECF) sigma factor and a redox-active anti-sigma factor. Known targets that aid in the protection and recovery from disulphide stress include the thioredoxin system and genes involved in producing the major thiol buffer mycothiol. Here we determine the global response to diamide in wild-type and sigR mutant backgrounds to understand the role of σR in this response and to reveal additional regulatory pathways that allow cells to cope with disulphide stress. In addition to thiol oxidation, diamide was found to cause protein misfolding and aggregation, which elicited the induction of the HspR heat-shock regulon. Although this response is σR-independent,σR does directly control Clp and Lon ATP-dependent AAA(+) proteases, which may partly explain the reduced ability of a sigR mutant to resolubilize protein aggregates.σR also controls msrA and msrB methionine sulphoxide reductase genes, implying that σR–RsrA is responsible for the maintenance of both cysteine and methionine residues during oxidative stress. This work shows that the σR–RsrA system plays a more significant role in protein quality control than previously realized, and emphasizes the importance of controlling the cellular thiol–disulphide redox balance.

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Crossref · 10.1099/mic.0.037804-0

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  • Adverse heart health outcomes are tied not only to shift work and circadian misalignment but also to psychological and psychosocial stressors.

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Authors
Kallifidas, D., Thomas, D., Doughty, P., & Paget, M. S. B.
Affiliations
University of Sussex (GB)
Venue
Microbiology
Published
2010-06-01
Volume
156
Issue
6
Pages
1661-1672
ISSN
  • 1350-0872 (ISSN-L)
  • 1465-2080
OpenAlex
W2101594254
Cited by
53
References
55
Citations by year
2026: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 9 · 2016: 3 · 2015: 6 · 2014: 3 · 2013: 5 · 2012: 5
FWCI
2.16
Type
journal article
Language
en
Open access
closed
Locations
  • Microbiology (publishedVersion)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion)
Funders
  • University of Surrey
  • Biotechnology and Biological Sciences Research Council (BB/C503854/1, P14618)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
Streptomyces coelicolor, diamide, protein quality control, protein misfolding, protein aggregation, Clp protease, Lon protease, AAA+ protease, methionine sulfoxide reductase, MsrA, MsrB, thioredoxin system, mycothiol, oxidative stress response, anti-sigma factor
MeSH terms
Bacterial Proteins, Diamide, Disulfides, Heat-Shock Proteins, Proteins, Repressor Proteins, RNA, Sigma Factor, Transcription Factors, Protein Folding, Regulon, Streptomyces coelicolor

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