Rajasekar, Karthik V., Zdanowski, Konrad, Yan, Jun et al. (10 more authors) (2016) The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core. Nature Communications. 12194. ISSN 2041-1723
Abstract
Redox-regulated effector systems that counteract oxidative stress are essential for all forms of life. Here we uncover a new paradigm for sensing oxidative stress centred on the hydrophobic core of a sensor protein. RsrA is an archetypal zinc-binding anti-sigma factor that responds to disulfide stress in the cytoplasm of Actinobacteria. We show that RsrA utilizes its hydrophobic core to bind the sigma factor σ R preventing its association with RNA polymerase, and that zinc plays a central role in maintaining this high-affinity complex. Oxidation of RsrA is limited by the rate of zinc release, which weakens the RsrA-σ R complex by accelerating its dissociation. The subsequent trigger disulfide, formed between specific combinations of RsrA's three zinc-binding cysteines, precipitates structural collapse to a compact state where all σ R-binding residues are sequestered back into its hydrophobic core, releasing σ R to activate transcription of anti-oxidant genes.
Metadata
Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2016 |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 13 Jun 2016 14:31 |
Last Modified: | 04 Feb 2024 00:42 |
Published Version: | https://doi.org/10.1038/ncomms12194 |
Status: | Published |
Refereed: | Yes |
Identification Number: | https://doi.org/10.1038/ncomms12194 |
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