Caister Academic Press

Thiol-based sensory factors

Haike Antelmann and Peter Zuber
from: Sensory Mechanisms in Bacteria: Molecular Aspects of Signal Recognition (Edited by: Stephen Spiro and Ray Dixon). Caister Academic Press, U.K. (2010)

Abstract

Bacteria regularly encounter Reactive Oxygen, Nitrogen and Electrophilic Species (ROS, RNS, RES) that are generated inside the cells by incomplete reduction of molecular oxygen, imbalanced metabolic processes or applied externally by toxic or antimicrobial compounds. The response to such reactive agents is mediated by redox-sensitive transcription factors that exploit the unique chemistry of cysteine thiol groups. Redox-sensitive regulatory proteins bear cysteine residues that can undergo post-translational modification, leading to either activation or inactivation of the transcription factors. This in turn results in responses that are aimed to detoxify the reactive species or alleviate the damage they cause. Different thiol-modifications are implicated in redox-sensing depending on the number of redox-active Cys residues and their reactivity, the oxidant to which they react, and the prevailing in vitro or in vivo conditions. Redox-sensitive proteins with more than one reactive Cys residue undergo in most cases reversible inter- and/or intramolecular disulfide linkages, which serve as sensing mechanisms for OxyR, the 2-Cys OhrR family, MexR, OspR, Spx, CprK and CrtJ. In contrast to these classical thiol-disulfide-switches, transcription factors with one redox-active Cys residue are reversibly regulated via initial sulphenic acid formation, S-thiolation with low molecular weight (LMW) thiols and sulfenamide formation with the backbone amide as shown for OxyR, the 1-Cys OhrR ortholog, MgrA and SarZ. However, the thiol group of the 1-Cys OhrR protein can also be irreversibly modified by overoxidation to sulfinic and sulfonic acids in response to strong oxidants. RES such as quinones were shown to modify the YodB repressor irreversibly by thiol-(S)-alkylation. In addition to redox-sensing transcription factors, LMW thiols and the thioredoxin/thioredoxin reductase system maintain the thiol-redox-balance of the cell upon exposure to reactive species. Here we review (1) enzymatic redox control mechanisms by thiol-disulfide reductases and (2) the current knowledge of bacterial redox-sensitive transcription factors that function without metal cofactors, including OxyR, OhrR, MexR, OspR, MgrA, SarZ, YodB, Spx, CprK and PspR/CrtJ. Each of these transcription factors senses unique signals including ROS, RNS, RES, antibiotic and haloorganic compounds, or the cellular oxygen level and light that are transduced via diverse redox-sensing mechanisms involving different reversible and irreversible thiol-modifications read more ...
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