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

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Structural basis for the redox sensitivity of the Mycobacterium tuberculosis SigK-RskA σ-anti-σ complex.
 
Creator Shukla, Jinal
Gupta, Radhika
Thakur, Krishan Gopal
Gokhale, Rajesh
Gopal, B
 
Subject QR Microbiology
 
Description 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) σ factor σ(K) governs the transcription of the serodominant antigens MPT70 and MPT83. The cellular levels of σ(K) are regulated by the membrane-associated anti-σ(K) (RskA) that localizes σ(K) in an inactive complex. The crystal structure of M. tuberculosis σ(K) in complex with the cytosolic domain of RskA (RskAcyto) revealed a disulfide bridge in the -35 promoter-interaction region of σ(K). Biochemical experiments reveal that the redox potential of the disulfide-forming cysteines in σ(K) is consistent with its role as a sensor. The disulfide bond in σ(K) influences the stability of the σ(K)-RskAcyto complex but does not interfere with σ(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.
 
Publisher Malden, MA : Wiley-Blackwell
 
Date 2014-04
 
Type Article
PeerReviewed
 
Relation http://scripts.iucr.org/cgi-bin/paper?S1399004714000121
http://crdd.osdd.net/open/1532/
 
Identifier 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 σ-anti-σ complex. Acta crystallographica. Section D, Biological crystallography, 70 (Pt 4). pp. 1026-36. ISSN 1399-0047