The C-terminal domain of M. tuberculosis ECF sigma factor I (SigI) interferes in SigI-RNAP interaction.

Mycobacterium tuberculosis is equipped with diversified ECF sigma factors that are generally expressed under adverse environmental conditions. Mtb-SigI belongs to the ECF41 family of sigma factor, and no information is available about their expression during stringent response. This study provides the structural insight of Mtb-SigI and the characterization of its C-terminal polypeptide extension. C-terminal site of Mtb-SigI is truncated in two ways: (a) conserved region of C-terminal extension is preserved while the rest of the portion is deleted and (b) complete deletion of C-terminal extension. Each of the wild-type and truncated Mtb-SigI is docked with a β subunit of core RNA polymerase and simulated for 100 ns. Relative binding strength calculated from trajectory analysis reflects that the complete deletion of the C-terminal extension of Mtb-SigI favors interaction with core RNA polymerase. It can be implicated that the C-terminal domain in the wild-type docked complex help flipping of domain 4 of Mtb-SigI and thereby impaired holoenzyme formation. When the C-terminal extension is partially deleted, such flipping of domain 4 of Mtb-SigI diminishes and complete deletion of C-terminal extension promotes holoenzyme formation. In the absence of any sigma factor antagonist, the C-terminal extension of Mtb-SigI might behave as a complex player in transcription regulation. Graphical abstract Role of Mtb-SigI in transcription regulation.