Determination of Redox Sensitivity in Structurally Similar Biological Redox Sensors

Jamithireddy, Anil K and Samajdar, Rudra N and Gopal, B and Bhattacharyya, Aninda J (2017) Determination of Redox Sensitivity in Structurally Similar Biological Redox Sensors. In: JOURNAL OF PHYSICAL CHEMISTRY B, 121 (29). pp. 7005-7015.

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Abstract

Redox stimuli govern a variety of biological processes. The relative sensitivity of redox sensors plays an important role in providing a calibrated response to environmental stimuli and cellular homeostasis. This cellular machinery plays a crucial role in the human pathogen Mycobacterium tuberculosis as it encounters diverse microenvironments in the host. The redox sensory mechanism in M. tuberculosis is governed by,two component and one-component systems, alongside a class of transcription factors called the extra cytoplasmic function (ECF) sigma factors. ECF sigma factors that govern the cellular response to redox stimuli are negatively regulated by forming a complex with proteins called zinc associated anti-sigma factors (ZAS). ZAS proteins release their cognate sigma factor in response to oxidative stress. The relative sensitivity of the ZAS sensors to redox processes dictate the concentration of free ECF sigma factors in the cell. However, factors governing the redox threshold of these sensors remain unclear. We describe here, the molecular characterization of three sigma factor/ZAS pairs sigma(L)/RslA, sigma(E)/RseA, and sigma(H)/RshA using a combination of biophysical and electrochemical techniques. This study reveals, conclusively, the differences in redox sensitivity in these proteins despite apparent structural similarity and rationalizes the hierarchy in the activation of the cognate ECF sigma factors. Put together, the study provides a basis for examining sequence and conformational features that modulate redox sensitivity within the confines of a conserved structural scaffold. The findings provide the guiding principles for the design of intracellular redox sensors with tailored sensitivity and predictable redox thresholds, providing a much needed biochemical tool for understanding host-pathogen interaction.

Item Type:	Journal Article
Publication:	JOURNAL OF PHYSICAL CHEMISTRY B
Additional Information:	Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited:	24 Aug 2017 06:06
Last Modified:	24 Aug 2017 06:06
URI:	http://eprints.iisc.ac.in/id/eprint/57665

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