Mycobacterium tuberculosis RbpA protein is a new type of transcriptional activator that stabilizes the σ A -containing RNA polymerase holoenzyme
Open Access
- 8 May 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 40 (14), 6547-6557
- https://doi.org/10.1093/nar/gks346
Abstract
RbpA is an RNA polymerase (RNAP)-binding protein whose presence increases the tolerance levels of Mycobacteria to the first-line anti-tuberculosis drug rifampicin by an unknown mechanism. Here, we show that the role of Mycobacterium tuberculosis RbpA in resistance is indirect because it does not affect the sensitivity of RNAP to rifampicin while it stimulates transcription controlled by the housekeeping σ A -factor. The transcription regulated by the stress-related σ F was not affected by RbpA. The binding site of RbpA maps to the RNAP β subunit Sandwich-Barrel Hybrid Motif, which has not previously been described as an activator target and does not overlap the rifampicin binding site. Our data suggest that RbpA modifies the structure of the core RNAP, increases its affinity for σ A and facilitates the assembly of the transcriptionally competent promoter complexes. We propose that RbpA is an essential partner which advantages σ A competitiveness for core RNAP binding with respect to the alternative σ factors. The RbpA-driven stimulation of the housekeeping gene expression may help Mycobacteria to tolerate high rifampicin levels and to adapt to the stress conditions during infection.Keywords
This publication has 55 references indexed in Scilit:
- Mechanism of Bacterial Transcription Initiation: RNA Polymerase - Promoter Binding, Isomerization to Initiation-Competent Open Complexes, and Initiation of RNA SynthesisJournal of Molecular Biology, 2011
- Resistance to rifampicin: at the crossroads between ecological, genomic and medical concernsInternational Journal of Antimicrobial Agents, 2010
- Probing DNA Binding, DNA Opening, and Assembly of a Downstream Clamp/Jaw in Escherichia coli RNA Polymerase−λPR Promoter Complexes Using Salt and the Physiological Anion GlutamateBiochemistry, 2010
- Molecular Evolution of Multisubunit RNA Polymerases: Sequence AnalysisJournal of Molecular Biology, 2009
- CarD Is an Essential Regulator of rRNA Transcription Required for Mycobacterium tuberculosis PersistenceCell, 2009
- Mycobacterium tuberculosis SigF Regulates Genes Encoding Cell Wall-Associated Proteins and Directly Regulates the Transcriptional Regulatory Gene phoY1Journal of Bacteriology, 2007
- Stationary phase reorganisation of the Escherichia coli transcription machinery by Crl protein, a fine-tuner of σs activity and levelsThe EMBO Journal, 2007
- Region 1.2 of the RNA polymerase σ subunit controls recognition of the −10 promoter elementThe EMBO Journal, 2007
- Crl Facilitates RNA Polymerase Holoenzyme FormationJournal of Bacteriology, 2006
- UCSF Chimera?A visualization system for exploratory research and analysisJournal of Computational Chemistry, 2004