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Structural and Biochemical Bases for the Redox Sensitivity of Mycobacterium tuberculosis RslA

Thakur, Krishan Gopal and Praveena, T and Gopal, B (2010) Structural and Biochemical Bases for the Redox Sensitivity of Mycobacterium tuberculosis RslA. In: Journal of Molecular Biology, 397 (5). pp. 1199-1208.

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Official URL: http://dx.doi.org/10.1016/j.jmb.2010.02.026


An effective transcriptional response to redox stimuli is of particular importance for Mycobacterium tuberculosis, as it adapts to the environment of host alveoli and macrophages. The M. tuberculosis a factor sigma(L) regulates the expression of genes involved in cell-wall and polyketide syntheses. sigma(L) interacts with the cytosolic anti-sigma domain of a membrane-associated protein, RslA. Here we demonstrate that RslA binds Zn2+ and can sequester sigma(L) in a reducing environment. In response to an oxidative stimulus, proximal cysteines in the CXXC motif of RslA form a disulfide bond, releasing bound Zn2+. This results in a substantial rearrangement of the sigma(L)/RslA complex, leading to an 8-fold decrease in the affinity of RslA for sigma(L). The crystal structure of the -35-element recognition domain of sigma(L), sigma(L)(4), bound to RslA reveals that RslA inactivates sigma(L) by sterically occluding promoter DNA and RNpolymerase binding sites. The crystal structure further reveals that the cysteine residues that coordinate Zn2+ in RslA are solvent exposed in the complex, thus providing a structural basis for the redox sensitivity of RslA. The biophysical parameters of sigma(L)/RslA interactions provide a template for understanding how variations in the rate of Zn2+ release and associated conformational changes could regulate the activity of a Zn2+-associated anti-sigma factor. (C) 2010 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Elsevier Science.
Keywords: extracytoplasmic function sigma factor;zinc binding;redox sensitivity;anti-sigma factor
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Ms G Yashodha
Date Deposited: 11 May 2010 12:18
Last Modified: 19 Sep 2010 06:06
URI: http://eprints.iisc.ac.in/id/eprint/27704

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