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Publication Abstract from PubMed

The host-pathogen interactions in Mycobacterium tuberculosis infection are significantly influenced by redox stimuli and alterations in the levels of secreted antigens. The extracytoplasmic 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)-RskAcyto 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.

Structural basis for the redox sensitivity of the Mycobacterium tuberculosis SigK-RskA sigma-anti-sigma complex.,Shukla J, Gupta R, Thakur KG, Gokhale R, Gopal B Acta Crystallogr D Biol Crystallogr. 2014 Apr 1;70(Pt 4):1026-36. doi:, 10.1107/S1399004714000121. Epub 2014 Mar 19. PMID:24699647^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.