Structural basis for the redox sensitivity of the Mycobacterium tuberculosis SigK-RskA sigma-anti-sigma complex

Shukla, Jinal and Gupta, Radhika and Thakur, Krishan Gopal and Gokhale, Rajesh and Gopal, B (2014) Structural basis for the redox sensitivity of the Mycobacterium tuberculosis SigK-RskA sigma-anti-sigma complex. In: ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 70 (4). pp. 1026-1036.

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Abstract

The host-pathogen interactions in Mycobacterium tuberculosis infection are significantly influenced by redox stimuli and alterations in the levels of secreted antigens. The extracyto-plasmic function (ECF) sigma factor sigma(K) governs the transcription of the serodominant antigens MPT70 and MPT83. The cellular levels of sigma(K) are regulated by the membrane-associated anti-sigma(K) (RskA) that localizes sigma(K) in an inactive complex. The crystal structure of M. tuberculosis sigma(K) in complex with the cytosolic domain of RskA (RskAcyto) revealed a disulfide bridge in the -35 promoter-interaction region of sigma(K). Biochemical experiments reveal that the redox potential of the disulfide-forming cysteines in sigma(K) is consistent with its role as a sensor. The disulfide bond in sigma(K) influences the stability of the sigma(K)-RskA(cyto) complex but does not interfere with sigma(K)-promoter DNA interactions. It is noted that these disulfide-forming cysteines are conserved across homologues, suggesting that this could be a general mechanism for redox-sensitive transcription regulation.

Item Type:	Journal Article
Publication:	ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
Publisher:	WILEY-BLACKWELL
Additional Information:	Copyright for this article belongs to the WILEY-BLACKWELL, USA
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	18 Jun 2014 05:56
Last Modified:	18 Jun 2014 05:56
URI:	http://eprints.iisc.ac.in/id/eprint/49018

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