Mycobacterium tuberculosis RbpA protein is a new type of transcriptional activator that stabilizes the σ A-containing RNA polymerase holoenzyme.

Nucleic Acids Research
Yangbo HuKonstantin Brodolin

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.

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Citations

Apr 23, 2013·Nucleic Acids Research·Aline Tabib-SalazarMark S Paget
Sep 14, 2014·Nucleic Acids Research·Jarmila HnilicováLibor Krásný
Oct 21, 2014·Expert Review of Proteomics·Tao Cui, Zheng-Guo He
Jun 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth A HubinMark S Paget
Sep 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Do-Hee KimBong-Jin Lee
Feb 18, 2016·Journal of Bacteriology·Kelly FlentieChristina L Stallings
Oct 30, 2018·Nucleic Acids Research·Klára ŠmídováJiri Vohradsky
May 29, 2018·Science Advances·Rishi Kishore VishwakarmaKonstantin Brodolin
Sep 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Michal StyczynskiLukasz Dziewit
Apr 4, 2013·The Journal of Biological Chemistry·Alessio BortoluzziHelen M O'Hare
Aug 28, 2020·Frontiers in Microbiology·Rishi Kishore Vishwakarma, Konstantin Brodolin
Oct 6, 2020·Frontiers in Bioengineering and Biotechnology·Gundeep KaurKrishan Gopal Thakur
Oct 31, 2020·Nature Reviews. Microbiology·James ChenElizabeth A Campbell
Mar 23, 2017·Protein Expression and Purification·Omar Herrera-AsmatMaria L Kireeva
Feb 20, 2021·Proceedings of the National Academy of Sciences of the United States of America·Marie DelabyPatrick H Viollier

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Methods Mentioned

BETA
cross-linking study
PCR
electrophoretic mobility shift assay
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Software Mentioned

ImageQuant
UCSF Chimera

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