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Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide-sensitive iron-sulfur cluster.
Smith, Laura J; Stapleton, Melanie R; Fullstone, Gavin J M; Crack, Jason C; Thomson, Andrew J; Le Brun, Nick E; Hunt, Debbie M; Harvey, Evelyn; Adinolfi, Salvatore; Buxton, Roger S; Green, Jeffrey.
Afiliação
  • Smith LJ; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK.
Biochem J ; 432(3): 417-27, 2010 Dec 15.
Article em En | MEDLINE | ID: mdl-20929442
ABSTRACT
Mycobacterium tuberculosis is a major pathogen that has the ability to establish, and emerge from, a persistent state. Wbl family proteins are associated with developmental processes in actinomycetes, and M. tuberculosis has seven such proteins. In the present study it is shown that the M. tuberculosis H37Rv whiB1 gene is essential. The WhiB1 protein possesses a [4Fe-4S]2+ cluster that is stable in air but reacts rapidly with eight equivalents of nitric oxide to yield two dinuclear dinitrosyl-iron thiol complexes. The [4Fe-4S] form of WhiB1 did not bind whiB1 promoter DNA, but the reduced and oxidized apo-WhiB1, and nitric oxide-treated holo-WhiB1 did bind to DNA. Mycobacterium smegmatis RNA polymerase induced transcription of whiB1 in vitro; however, in the presence of apo-WhiB1, transcription was severely inhibited, irrespective of the presence or absence of the CRP (cAMP receptor protein) Rv3676, which is known to activate whiB1 expression. Footprinting suggested that autorepression of whiB1 is achieved by apo-WhiB1 binding at a region that overlaps the core promoter elements. A model incorporating regulation of whiB1 expression in response to nitric oxide and cAMP is discussed with implications for sensing two important signals in establishing M. tuberculosis infections.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Fatores de Transcrição / Proteínas de Ligação a DNA / Proteínas Ferro-Enxofre / Mycobacterium tuberculosis / Óxido Nítrico Tipo de estudo: Diagnostic_studies / Prognostic_studies Idioma: En Ano de publicação: 2010 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Fatores de Transcrição / Proteínas de Ligação a DNA / Proteínas Ferro-Enxofre / Mycobacterium tuberculosis / Óxido Nítrico Tipo de estudo: Diagnostic_studies / Prognostic_studies Idioma: En Ano de publicação: 2010 Tipo de documento: Article