| Structural highlights
Function
[RSRA_STRCO] A redox-regulated anti-sigma factor for extracytoplasmic function (ECF) sigma factor SigR, and a key sensor of disulfide stress. Holds SigR, its cognate ECF sigma factor, in an inactive form, inhibiting its sigma activity under reducing but not oxidizing conditions; oxidation and reduction of the anti-sigma factor is reversible. Mycothiol (MSH) is competent for reduction of RsrA, allowing it to bind to SigR. In conjunction with its cognate sigma factor SigR may sense the intracellular level of reduced MSH. Probably releases SigR during oxidative stress.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
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 sigma(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-sigma(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 sigma(R)-binding residues are sequestered back into its hydrophobic core, releasing sigma(R) to activate transcription of anti-oxidant genes.
The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core.,Rajasekar KV, Zdanowski K, Yan J, Hopper JT, Francis ML, Seepersad C, Sharp C, Pecqueur L, Werner JM, Robinson CV, Mohammed S, Potts JR, Kleanthous C Nat Commun. 2016 Jul 19;7:12194. doi: 10.1038/ncomms12194. PMID:27432510[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kang JG, Paget MS, Seok YJ, Hahn MY, Bae JB, Hahn JS, Kleanthous C, Buttner MJ, Roe JH. RsrA, an anti-sigma factor regulated by redox change. EMBO J. 1999 Aug 2;18(15):4292-8. PMID:10428967 doi:http://dx.doi.org/10.1093/emboj/18.15.4292
- ↑ Paget MS, Bae JB, Hahn MY, Li W, Kleanthous C, Roe JH, Buttner MJ. Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a thiol-disulphide redox switch. Mol Microbiol. 2001 Feb;39(4):1036-47. PMID:11251822
- ↑ Li W, Stevenson CE, Burton N, Jakimowicz P, Paget MS, Buttner MJ, Lawson DM, Kleanthous C. Identification and structure of the anti-sigma factor-binding domain of the disulphide-stress regulated sigma factor sigma(R) from Streptomyces coelicolor. J Mol Biol. 2002 Oct 18;323(2):225-36. PMID:12381317
- ↑ Li W, Bottrill AR, Bibb MJ, Buttner MJ, Paget MS, Kleanthous C. The Role of zinc in the disulphide stress-regulated anti-sigma factor RsrA from Streptomyces coelicolor. J Mol Biol. 2003 Oct 17;333(2):461-72. PMID:14529630 doi:http://dx.doi.org/10.1016/S0022283603010763
- ↑ Park JH, Roe JH. Mycothiol regulates and is regulated by a thiol-specific antisigma factor RsrA and sigma(R) in Streptomyces coelicolor. Mol Microbiol. 2008 May;68(4):861-70. doi: 10.1111/j.1365-2958.2008.06191.x. PMID:18430082 doi:http://dx.doi.org/10.1111/j.1365-2958.2008.06191.x
- ↑ Rajasekar KV, Zdanowski K, Yan J, Hopper JT, Francis ML, Seepersad C, Sharp C, Pecqueur L, Werner JM, Robinson CV, Mohammed S, Potts JR, Kleanthous C. The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core. Nat Commun. 2016 Jul 19;7:12194. doi: 10.1038/ncomms12194. PMID:27432510 doi:http://dx.doi.org/10.1038/ncomms12194
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