Structural analysis of alternate sigma factor ComX with RpoC, RpoB and its cognate CIN promoter reveals a distinctive promoter melting mechanism

Abstract

Alternate sigma factors play a major role in the survival of pathogenic bacteria such as Streptococcus pyogenes in adverse environment conditions. Stress induced sigma factors mediate gene expression under conditions of pathogenesis, dormancy and unusual environmental cues. In the present work, ComX, an alternate sigma factor from S. pyogenes has been characterized. The structures of ComX, RpoB β subunit and RpoC β’ subunit of RNA polymerase have been predicted using comparative and homology modelling respectively and validated. Attempts have been made to study RpoB-RpoC-ComX complex interactions with Double Strand (DS) and Single Strand (SS) pro

moter regions. Stability of these complexes and the promoter melting mechanism have been analysed using Molecular Dynamic (MD) simulations. This study suggests that ComX, although identifies promoter analogous to the alternate sigma factor SigH of M. tuberculosis, follows a distinctive promoter flip out mechanism.

Communicated by Ramaswamy H. Sarma

Keywords:

• Alternate sigma factor
• RNA polymerase
• protein-protein docking
• protein–DNA docking

Acknowledgements

We gratefully acknowledge Science and Engineering Research Board (SERB), Government of India for financial support. PR thanks DST-FIST, Government of India for the computational facilities sanctioned to the department (No: SR/FST/LSII-037/2014 (C) dt. 29.03.2016).