%A Jinal Shukla
%A Radhika Gupta
%A Krishan Gopal Thakur
%A Rajesh Gokhale
%A B Gopal
%J Acta crystallographica. Section D, Biological crystallography
%T Structural basis for the redox sensitivity of the Mycobacterium tuberculosis SigK-RskA ?-anti-? complex.
%X 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) ? factor ?(K) governs the transcription of the serodominant antigens MPT70 and MPT83. The cellular levels of ?(K) are regulated by the membrane-associated anti-?(K) (RskA) that localizes ?(K) in an inactive complex. The crystal structure of M. tuberculosis ?(K) in complex with the cytosolic domain of RskA (RskAcyto) revealed a disulfide bridge in the -35 promoter-interaction region of ?(K). Biochemical experiments reveal that the redox potential of the disulfide-forming cysteines in ?(K) is consistent with its role as a sensor. The disulfide bond in ?(K) influences the stability of the ?(K)-RskAcyto complex but does not interfere with ?(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.
%N Pt 4
%K transcription; redox sensitivity; secreted antigens; extracytoplasmic function [sigma] factors.
%P 1026-36
%V 70
%D 2014
%I Malden, MA : Wiley-Blackwell
%L open1532