Molecular regulation of Mycobacterium tuberculosis Sigma factor H with Anti-sigma factor RshA under stress condition

Sayantee Sen; Swarnav Bhakta; Kuntal Pal

doi:10.18006/2024.12(1).153.162

Authors

Sayantee Sen Department of Biotechnology, Adamas University, West Bengal, India https://orcid.org/0009-0006-1025-2430
Swarnav Bhakta Department of Developmental Biology, Agharkar Research Institute, Pune 411004, India https://orcid.org/0000-0001-6047-2382
Kuntal Pal Department of Bioscience, School of Bio Sciences and Technology, Vellore Institute of Technology, Tamil Nadu 632014, India https://orcid.org/0000-0001-7094-2456

DOI:

https://doi.org/10.18006/2024.12(1).153.162

Keywords:

Sigma Factor, SigH, Anti-sigma factor, RshA, Mycobacterium tuberculosis, Bacterial transcription

Abstract

Mycobacterium tuberculosis is the causative agent of tuberculosis, the leading fatal infectious disease that claims millions of lives every year. M. tuberculosis regulates its stress condition response using its regulatory protein, Sigma Factor H, which binds with its cognate anti-sigma factor RshA in normal conditions, forming a complex inhibiting transcription. During oxidative stress, SigH is released from the complex and binds to RNA Polymerase (RNAP) to initiate transcription. Thus, it is important to understand the molecular conformational state of SigH in complex with different protein partners under different cellular or environmental contexts. This work intends to analyze the SigH-RshA complex, which revealed the variation in SigH shown during complex formation with RNAP and RshA, respectively. Previously, Hydrogen Deuterium Exchange-Mass Spectrometry (HDX-MS) analysis of SigH-RshA interaction provided a detailed insight into the critical residues participating in the interaction. The HDX-MS data were used to dock RshA on the open conformation of SigH from the SigH-RNAP complex structure (PDB: 5ZX2), and closed conformation was obtained from protein modelling. The docking revealed that closed conformation of SigH complexing with RshA in terms of HDX-MS data revealed a major structural shift in SigH while interacting with two different binding partners, RshA and RNAP, under variable environmental conditions. This structural shift of SigH with RshA and RNAP has significance in understanding the stress response of M. tuberculosis, and SigH could prove to be a potential drug target.

Author Biographies

Swarnav Bhakta, Department of Developmental Biology, Agharkar Research Institute, Pune 411004, India

Department of Biotechnology, Adamas University, West Bengal, India

Kuntal Pal, Department of Bioscience, School of Bio Sciences and Technology, Vellore Institute of Technology, Tamil Nadu 632014, India

Department of Biotechnology, Adamas University, West Bengal, India

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