PUBLICATION IN SCIENCE ADVANCES (IF=11.5)

Konstantin BRODOLIN publishes an article in Science Advances (IF=11.5): Single-molecule analysis reveals the mechanism of transcription activation in Mycobacterium tuberculosis (Vishwakarma et al, 2018)

http://advances.sciencemag.org.insb.bib.cnrs.fr/content/4/5/eaao5498

The sigma subunit of bacterial RNA polymerase (RNAP) controls recognition of the -10 and -35 promoter elements during transcription initiation. Free sigma adopts a “closed”, inactive, conformation incompatible with promoter binding. The conventional two-state model of sigma activation proposes that binding to core RNAP induces formation of an “open”, active, sigma conformation which is optimal for promoter recognition. Here, using single-molecule Forster resonance energy transfer (smFRET), we demonstrate that vegetative-type sigma subunits exist in open and closed states even after binding to the RNAP core. As an extreme case, RNAP from Mycobacterium tuberculosis, preferentially retains sigma in the closed conformation, which is converted to the open conformation only upon binding by the activator protein RbpA and interaction with promoter DNA. These findings reveal that the conformational dynamics of the sigma subunit in RNAP holoenzyme is a target for regulation by transcription factors and plays a critical role in promoter recognition.