Journal of Signal Transduction

Review Article

ROS-Mediated Signalling in Bacteria: Zinc-Containing Cys-X-X-Cys Redox Centres and Iron-Based Oxidative Stress

Table 1

Examples of proteins containing the redox-sensing motif Cys-X-X-Cys. (*) The references given are for the protein from the strain listed. Sequence alignments demonstrate that highly homologous proteins are found across many different bacterial species.


	Name	Strain*	Function	Zn²⁺-binding

Enzymatic function	Hsp33	Escherichia coli	The redox-regulated heat shock protein Hsp33 is a dual stress sensor responding to peroxide stress and increased temperature. Stress-mediated conformational changes result in zinc release and activation of Hsp33 chaperone function leading to suppression of protein aggregation [18].	Yes
	Trx2	Escherichia coli	Trx2 reductase activity is controlled by a redox switch within two CXXC motifs involved in zinc binding. Release of the bound zinc ion results in a conformational change leading to the reductase activity [23].	Yes
	ResA	Bacillus subtilis	Substrate selection of the membrane-bound thiol-disulfide oxidoreductase ResA is regulated by conformational changes determined by CXXC reduction or oxidation [24].	No
	DsbA	Escherichia coli	DsbA is a periplasmic protein oxidant for disulfide formation of extracellular proteins belonging to the Dsb family [25].	No
	SbcC	Bacillus subtilis	SbcC is a DNA repair protein with exonuclease activity [27].	Yes
	Cytochrome c	Bacillus subtilis	The covalent coordination of heme to apo-cytochrome c requires a reduced CXXC motif within the heme-binding motif [28].	No
	AhpF/AhpC	Salmonella typhimurium	AhpC and flavoprotein AhpF catalyze the pyridine nucleotide-dependent reduction of hydroperoxide substrates. AhpC, the peroxide-reducing component, is a scavenger of hydrogen peroxide in bacteria, whereas the disulfide reductase protein AhpF regenerates AhpC [29].	No
	CopA	Thermotoga maritima	CopA, a copper transport ATPase, sustains important roles in homeostasis of heavy metals and delivery of copper to metalloenzymes [30].	No
	HypA	Escherichia coli	HypA is required for nickel insertion into the hydrogenase precursor proteins [31].	No

Transcriptional regulator	FurS	Streptomyces reticuli	Oxidation of the transcriptional repressor FurS leads to derepression of the transcription of the gene cpeB coding for a catalase peroxidase [6].	Yes
	CatR	Streptomyces coelicolor A3 (2)	During peroxide stress, the Fur-like regulator CatR activates transcription of catA coding for catalase A [21].	No
	WhiB3	Mycobacterium tuberculosis	WhiB3 DNA binding to control the expression of genes coding for polyketide synthases is reversibly regulated by a thiol-disulfide redox switch. Reduction of the apo-WhiB3 Cys thiols of the CXXC motif suppresses genes regulating the synthesis of complex lipids, whereas oxidation stimulates it [22].	No
	SoxR	Escherichia coli	SoxR senses superoxide stress through a CXXC-coordinated [2Fe-2S]-cluster that results in transcriptional activation of a superoxide response regulon [32].	No
	SurR	Pyrococcus furiosus (Archaea)	A redox switch regulates the transcriptional regulator SurR. Oxidation with S⁰ inhibits DNA binding by SurR, leading to repression of genes related to H₂ production and activation of genes involved in S⁰ metabolism [33].	No

Regulatory element	Spx	Bacillus subtilis	Global oxidative stress regulator interacting with the α-subunit of RNA polymerase for transcriptional induction of genes involved in thiol homeostasis (mrsA-mrsB operon) [19].	No
	RsrA	Streptomyces coelicolor A3 (2)	Antisigma factor RsrA negatively regulates expression of the thioredoxin system in response to cytoplasmatic oxidative stress. Under reducing conditions, RsrA binds to σ ^R resulting in inhibition of transcription [20].	Yes
	RslA	Mycobacterium tuberculosis	Membrane-associated RslA oxidation results in the release of bound Zn²⁺ through disulfide bond formation within the CXXC motif. The resulting conformational change leads to decreased σ ^L binding. The released sigma factor regulates the expression of genes involved in cell-wall and polyketide synthesis [17].	Yes
	RshA	Mycobacterium tuberculosis	RshA is an antisigma factor of the central regulator SigH that responds to oxidative and heat stress; it functions as a negative regulator of the alternative sigma factor SigH activity under reducing conditions [26].	No