Characterization of a putative ArsR transcriptional regulator encoded by <i>Rv2642</i> from <i>Mycobacterium tuberculosis</i>

Li, Chunyan; Xie, Longxiang; Zhang, Chenhui; Feng, Yonghong; Xie, Jianping

doi:10.1080/07391102.2016.1206037

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…13 ). Assuming multiple ArsR-type paralogs within an organism arise from gene duplication during evolution (like M. tuberculosis , which contains 12 putative ArsR-SmtB regulators 60 , 61 ), it seems likely that the Cys105 residue is present in an ancestral ArsR sequence and is an evolutionary remnant in RexT homologs. On the other hand, the phylogenetic tree suggests that the Cys40 residue may be a gain of function for the Nostocales organisms, which unlike Synechococcoles and Oscillatoriales , use heterocysts for nitrogen fixation and require thioredoxin to maintain an anaerobic environment (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Structural and mechanistic basis for redox sensing by the cyanobacterial transcription regulator RexT

Liu

et al. 2022

Commun Biol

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Organisms have a myriad of strategies for sensing, responding to, and combating reactive oxygen species, which are unavoidable consequences of aerobic life. In the heterocystous cyanobacterium Nostoc sp. PCC 7120, one such strategy is the use of an ArsR-SmtB transcriptional regulator RexT that senses H2O2 and upregulates expression of thioredoxin to maintain cellular redox homeostasis. Different from many other members of the ArsR-SmtB family which bind metal ions, RexT has been proposed to use disulfide bond formation as a trigger to bind and release DNA. Here, we present high-resolution crystal structures of RexT in the reduced and H2O2-treated states. These structures reveal that RexT showcases the ArsR-SmtB winged-helix-turn-helix fold and forms a vicinal disulfide bond to orchestrate a response to H2O2. The importance of the disulfide-forming Cys residues was corroborated using site-directed mutagenesis, mass spectrometry, and H2O2-consumption assays. Furthermore, an entrance channel for H2O2 was identified and key residues implicated in H2O2 activation were pinpointed. Finally, bioinformatics analysis of the ArsR-SmtB family indicates that the vicinal disulfide “redox switch” is a unique feature of cyanobacteria in the Nostocales order, presenting an interesting case where an ArsR-SmtB protein scaffold has been evolved to showcase peroxidatic activity and facilitate redox-based regulation.

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Section: Discussionmentioning

confidence: 99%

Structural and mechanistic basis for redox sensing by the cyanobacterial transcription regulator RexT

Liu

et al. 2022

Commun Biol

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“…Interestingly the expression of these genes is regulated by at least one of the ≈15 ArsR family proteins in Mtb . The considerable functional diversity of characterized ArsR proteins (SmtB (102), KmtR (103), CmtR (75), NmtR (104), Rv0081 (78), Rv2034 (72) and Rv2642(105)) coupled with sulfide-dependent regulation of dormancy genes and the possibility of more than one persulfide sensor suggests that bacteria such as Mtb may well incorporate a significant level of complexity or crosstalk between regulators. Thus, during infection, the signal triggered by different regulators that respond to persulfide, transition metal ion or peroxide signaling may be integrated into a single biological outcome (106, 107).…”

Section: Discussionmentioning

confidence: 99%

Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation inVibrio cholerae

Diez

Antelo

Dalia

et al. 2023

Preprint

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In vertebrates, host's immune system and resident commensal bacteria deploy a range of highly reactive small molecules that provide a barrier against microbial pathogens, including those known to induce oxidative and sulfide stress. Gut pathogens, such as Vibrio cholerae, sense and respond to these stressors by modulating the expression of exotoxins that are crucial for colonization. Here, we employ mass-spectrometry-based profiling, metabolomics, expression assays and biophysical approaches to show that transcriptional activation of the hemolysin gene hlyA in V. cholerae is regulated by intracellular RSS (reactive sulfur species, specifically sulfane sulfur). We first report a sequence similarity network analysis of the arsenic repressor (ArsR) superfamily of transcriptional regulators where RSS and ROS (reactive oxygen species) sensors segregate into distinct clusters. We show that HlyU, transcriptional activator of hlyA in V. cholerae, belongs to the RSS-sensing cluster and readily reacts with organic persulfides, showing no reactivity and remaining DNA-bound following treatment with various ROS in vitro, including H2O2. Surprisingly, in V. cholerae cell cultures both sulfide and peroxide treatment downregulate HlyU-dependent transcriptional activation of hlyA. However, RSS metabolite profiling showed that both sulfide and peroxide treatment raise the endogenous inorganic sulfide and disulfide levels to a similar extent, accounting for this crosstalk, and confirming that V. cholerae attenuates HlyU-mediated activation of hlyA in a specific response to intracellular RSS. These findings provide new evidence that gut pathogens may harness RSS-sensing as an evolutionary adaptation that allows them to overcome the gut inflammatory response by modulating the expression of exotoxins.

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“…Sequences within certain clusters in the network were assigned a putative function based on the information provided by their genome neighborhood, the conservation of key sequence motives within a cluster such as the DNA-binding residues ( 51 ) or the ligand-binding residues ( 55 ), and the regulatory function of characterized ArsRs that mapped within that cluster. Previously biochemically characterized ArsR family proteins ( Table S2 ) 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 were found in the network by manually searching for their UniProt ID in Cytoscape.…”

Section: Methodsmentioning

confidence: 99%

“…This article contains supporting information ( 33 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 ).…”

Section: Supporting Informationunclassified

Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation in Vibrio cholerae

Pis Diez,

Antelo,

Dalia

et al. 2023

Journal of Biological Chemistry

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Characterization of a putative ArsR transcriptional regulator encoded by Rv2642 from Mycobacterium tuberculosis

Cited by 10 publications

References 33 publications

Structural and mechanistic basis for redox sensing by the cyanobacterial transcription regulator RexT

Structural and mechanistic basis for redox sensing by the cyanobacterial transcription regulator RexT

Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation inVibrio cholerae

Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation in Vibrio cholerae

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