creators_name: Shukla, Jinal
creators_name: Gupta, Radhika
creators_name: Thakur, Krishan Gopal
creators_name: Gokhale, Rajesh
creators_name: Gopal, B
type: article
datestamp: 2015-01-27 09:47:29
lastmod: 2015-01-27 09:47:29
metadata_visibility: show
title: Structural basis for the redox sensitivity of the Mycobacterium tuberculosis SigK-RskA σ-anti-σ complex.
ispublished: pub
subjects: QR
keywords: transcription; redox sensitivity; secreted antigens; extracytoplasmic function [sigma] factors.
abstract: 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.
date: 2014-04
date_type: published
publication: Acta crystallographica. Section D, Biological crystallography
volume: 70
number: Pt 4
publisher: Malden, MA : Wiley-Blackwell
pagerange: 1026-36
refereed: TRUE
issn: 1399-0047
official_url: http://scripts.iucr.org/cgi-bin/paper?S1399004714000121
citation:   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