title: New family of tungstate-responsive transcriptional regulators in sulfate-reducing bacteria.
abstract: The trace elements molybdenum and tungsten are essential components of cofactors of many metalloenzymes. However, in sulfate-reducing bacteria, high concentrations of molybdate and tungstate oxyanions inhibit growth, thus requiring the tight regulation of their homeostasis. By a combination of bioinformatic and experimental techniques, we identified a novel regulator family, tungstate-responsive regulator (TunR), controlling the homeostasis of tungstate and molybdate in sulfate-reducing deltaproteobacteria. The effector-sensing domains of these regulators are similar to those of the known molybdate-responsive regulator ModE, while their DNA-binding domains are homologous to XerC/XerD site-specific recombinases. Using a comparative genomics approach, we identified DNA motifs and reconstructed regulons for 40 TunR family members. Positional analysis of TunR sites and putative promoters allowed us to classify most TunR proteins into two groups: (i) activators of modABC genes encoding a high-affinity molybdenum and tungsten transporting system and (ii) repressors of genes for toluene sulfonate uptake (TSUP) family transporters. The activation of modA and modBC genes by TunR in Desulfovibrio vulgaris Hildenborough was confirmed in vivo, and we discovered that the activation was diminished in the presence of tungstate. A predicted 30-bp TunR-binding motif was confirmed by in vitro binding assays. A novel TunR family of bacterial transcriptional factors controls tungstate and molybdate homeostasis in sulfate-reducing deltaproteobacteria. We proposed that TunR proteins participate in protection of the cells from the inhibition by these oxyanions. To our knowledge, this is a unique case of a family of bacterial transcriptional factors evolved from site-specific recombinases.
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Alexey E
authors.initials: AE
authors.lastname: Kazakov
authors.forename: Lara
authors.initials: L
authors.lastname: Rajeev
authors.forename: Eric G
authors.initials: EG
authors.lastname: Luning
authors.forename: Grant M
authors.initials: GM
authors.lastname: Zane
authors.forename: Kavya
authors.initials: K
authors.lastname: Siddartha
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Rodionov
authors.forename: Inna
authors.initials: I
authors.lastname: Dubchak
authors.forename: Adam P
authors.initials: AP
authors.lastname: Arkin
authors.forename: Judy D
authors.initials: JD
authors.lastname: Wall
authors.forename: Aindrila
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Pavel S
authors.initials: PS
authors.lastname: Novichkov
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005075:Biological Evolution; D003001:Cloning, Molecular; D003901:Desulfovibrio / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D008982:Molybdenum; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017973:Tungsten Compounds / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D014157:Transcription Factors; D017973:Tungsten Compounds; D008982:Molybdenum; C045951:tungstate
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