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Evaluation of specificity determinants in Mycobacterium tuberculosis �/anti-� factor interactions

Jamithireddy, AK and Runthala, A and Gopal, B (2020) Evaluation of specificity determinants in Mycobacterium tuberculosis �/anti-� factor interactions. In: Biochemical and Biophysical Research Communications, 521 (4). pp. 900-906.

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Official URL: https://doi.org/10.1016/j.bbrc.2019.10.198


Extra Cytoplasmic Function (ECF) σ factor/regulatory protein (anti-σ factor) pairs govern environment mediated changes in gene expression in bacteria. The release of the ECF σ factor from an inactive σ/anti-σ factor complex is triggered by specific environmental stimuli. The free σ factor then associates with the RNA polymerase and drives the expression of genes in its target regulon. Multiple ECF σ/anti-σ pairs ensure calibrated changes in the expression profile by correlating diverse environmental stimuli with changes in the intracellular levels of different ECF σ factors. Specificity in σ/anti-σ factor interaction is thus essential for accurate signal transduction. Here we describe experiments to evaluate interactions between different M. tuberculosis σ and anti-σ proteins in vitro. The interaction parameters suggest that cross-talk between non-cognate σ/anti-σ pairs is likely. The sequence and conformational determinants that govern interaction specificity in a σ/anti-σ complex are not immediately evident due to substantial structural conservation. Sequence-structure analysis of all σ/anti-σ pairs suggest that conserved residues are not the primary determinants of σ/anti-σ interactions-a finding that suggests a potential route to set tolerance limits in interaction specificity. Non-specific σ/anti-σ interactions are likely to be biologically significant as it can contribute to heterogeneity in cellular responses in a bacterial population under less stringent requirements. This finding is relevant for synthetic biology approaches to engineer bacteria using σ/anti-σ transcription initiation modules for diverse applications in biotechnology

Item Type: Journal Article
Publication: Biochemical and Biophysical Research Communications
Publisher: Elsevier B.V.
Additional Information: The copyright for this article belongs to the Elsevier B.V.
Keywords: bacterial protein; sigma factor, chemistry; circular dichroism; computer simulation; genetics; metabolism; Mycobacterium tuberculosis; protein domain; surface plasmon resonance, Bacterial Proteins; Circular Dichroism; Computer Simulation; Mycobacterium tuberculosis; Protein Interaction Domains and Motifs; Sigma Factor; Surface Plasmon Resonance
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 02 Feb 2023 09:58
Last Modified: 02 Feb 2023 09:58
URI: https://eprints.iisc.ac.in/id/eprint/79766

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