The σ R regulon of Streptomyces coelicolor A3(2) reveals a key role in protein quality control during disulphide stress
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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Adverse heart health outcomes are tied not only to shift work and circadian misalignment but also to psychological and psychosocial stressors.
“However, adverse heart health outcomes seem to be tied not only to shift work and circadian misalignment, but also the presence of psychological and psychosocial stressors [80,81].”
From Shift Work: Disrupted Circadian Rhythms and Sleep—Implications for Health and Well-being (2017) · cites this paper as [81]
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Shift Work: Disrupted Circadian Rhythms and Sleep—Implications for Health and Well-being
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- Authors
- Kallifidas, D., Thomas, D., Doughty, P., & Paget, M. S. B.
- Affiliations
- University of Sussex (GB)
- ORCID
- Paget, Mark S. B.
- Venue
- Microbiology
- Publisher
- Microbiology Society
- 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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