title: Mycobacterium tuberculosis RNA polymerase-binding protein A (RbpA) and its interactions with sigma factors.
abstract: RNA polymerase-binding protein A (RbpA), encoded by Rv2050, is specific to the actinomycetes, where it is highly conserved. In the pathogen Mycobacterium tuberculosis, RbpA is essential for growth and survival. RbpA binds to the β subunit of the RNA polymerase where it activates transcription by unknown mechanisms, and it may also influence the response of M. tuberculosis to the current frontline anti-tuberculosis drug rifampicin. Here we report the solution structure of RbpA and identify the principle sigma factor σ(A) and the stress-induced σ(B) as interaction partners. The protein has a central ordered domain with a conserved hydrophobic surface that may be a potential protein interaction site. The N and C termini are highly dynamic and are involved in the interaction with the sigma factors. RbpA forms a tight complex with the N-terminal domain of σ(B) via its N- and C-terminal regions. The interaction with sigma factors may explain how RbpA stabilizes sigma subunit binding to the core RNA polymerase and thereby promotes initiation complex formation. RbpA could therefore influence the competition between principal and alternative sigma factors and hence the transcription profile of the cell.
authors.affiliation: Department of Biochemistry, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Alessio
authors.initials: A
authors.lastname: Bortoluzzi
authors.affiliation: Department of Biochemistry, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Muskett
authors.affiliation: Department of Biochemistry, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Lorna C
authors.initials: LC
authors.lastname: Waters
authors.affiliation: Department of Biochemistry, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Addis
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rieck
authors.affiliation: Department of Cell and Molecular Biology, Leibniz Institute for Natural Product Research and Infection Biology e.V.-Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Munder
authors.affiliation: Department of Cell and Molecular Biology, Leibniz Institute for Natural Product Research and Infection Biology e.V.-Hans Knöll Institute, D-07745 Jena, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schleier
authors.affiliation: Dipartimento di BioScienze, Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Forti
authors.affiliation: Dipartimento di BioScienze, Università degli Studi di Milano, 20133 Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ghisotti
authors.affiliation: Department of Biochemistry, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom. Electronic address: mdc12@le.ac.uk.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Carr
authors.affiliation: Department of Biochemistry, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom; Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 9HN, United Kingdom. Electronic address: hmo7@le.ac.uk.
authors.forename: Helen M
authors.initials: HM
authors.lastname: O'Hare
mesh_terms: D039903:Actinobacteria / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D005816:Genetic Complementation Test; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012808:Sigma Factor / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D001426:Bacterial Proteins; D012808:Sigma Factor; D015534:Trans-Activators; C063505:RNA polymerase sigma A; D012321:DNA-Directed RNA Polymerases
keywords: Mycobacterium tuberculosis; NMR; Protein Structure; RNA Polymerase; RbpA; Sigma Factor; Transcription; Tuberculosis
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