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

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Author(s)

  • 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

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Publication details

JournalNature Communications
DateAccepted/In press - 8 Jun 2016
DatePublished (current) - 19 Jul 2016
Volume7
Number of pages14
Original languageEnglish

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.

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