The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core

Karthik V.  Rajasekar; Konrad Zdanowski; Jun  Yan; Jonathan T.S.  Hopper; Marie-Louise R.  Francis; Colin  Seepersad; Connor  Sharp; Ludovic  Pecqueur; Jorn M.  Werner; Carol V.  Robinson; Shabaz  Mohammed; Jennifer Robyn Potts; Colin  Kleanthous

doi:10.1038/ncomms12194

The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core

Karthik V. Rajasekar, Konrad Zdanowski, Jun Yan, Jonathan T.S. Hopper, Marie-Louise R. Francis, Colin Seepersad, Connor Sharp, Ludovic Pecqueur, Jorn M. Werner, Carol V. Robinson, Shabaz Mohammed, Jennifer Robyn Potts, Colin Kleanthous

Biology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	12194
Number of pages	14
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12194
Publication status	Published - 19 Jul 2016

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Rajasekar, K. V., Zdanowski, K., Yan, J., Hopper, J. T. S., Francis, M.-L. R., Seepersad, C., Sharp, C., Pecqueur, L., Werner, J. M., Robinson, C. V., Mohammed, S., Potts, J. R., & Kleanthous, C. (2016). The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core. Nature Communications, 7, Article 12194. https://doi.org/10.1038/ncomms12194

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AU - Francis, Marie-Louise R.

AU - Seepersad, Colin

AU - Sharp, Connor

AU - Pecqueur, Ludovic

AU - Werner, Jorn M.

AU - Robinson, Carol V.

AU - Mohammed, Shabaz

AU - Potts, Jennifer Robyn

AU - Kleanthous, Colin

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The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core

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