Structural and biochemical bases for the redox sensitivity of Mycobacterium tuberculosis RslA

Thakur, Krishan Gopal ; Praveena, T. ; Gopal, B. (2010) Structural and biochemical bases for the redox sensitivity of Mycobacterium tuberculosis RslA Journal of Molecular Biology, 397 (5). pp. 1199-1208. ISSN 0022-2836

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

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

Abstract

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 σ factor σL regulates the expression of genes involved in cell-wall and polyketide syntheses. σL interacts with the cytosolic anti-σ domain of a membrane-associated protein, RslA. Here we demonstrate that RslA binds Zn2+ and can sequester σL 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 σL/RslA complex, leading to an 8-fold decrease in the affinity of RslA for σL. The crystal structure of the − 35-element recognition domain of σL, σ4L, bound to RslA reveals that RslA inactivates σL by sterically occluding promoter DNA and RNA polymerase 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 σL/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-σ factor.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Extracytoplasmic Function σ Factor; Zinc binding; Redox Sensitivity; Anti-σ Factor
ID Code:98263
Deposited On:06 May 2014 11:38
Last Modified:06 May 2014 11:38

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