Structural basis for the redox sensitivity of the Mycobacterium tuberculosis SigK-RskA σ-anti-σ complex.
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.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
Jinal
J
Shukla
Institute of Genomics and Integrative Biology, New Delhi, India.
Radhika
R
Gupta
Institute of Microbial Technology, Chandigarh, India.
Krishan Gopal
KG
Thakur
Institute of Genomics and Integrative Biology, New Delhi, India.
Rajesh
R
Gokhale
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
B
B
Gopal
D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D012097:Repressor Proteins; D014157:Transcription Factors
extracytoplasmic function σ factors; redox sensitivity; secreted antigens; transcription