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Treponema denticola TroR is a manganese- and iron-dependent transcriptional repressor.

Brett PJ, Burtnick MN, Fenno JC, Gherardini FC - Mol. Microbiol. (2008)

Bottom Line: Interestingly, unlike the T. pallidum orthologue, T. denticola TroR (TroR(Td)) possesses a C-terminal Src homology 3-like domain commonly associated with DtxR family members.In addition, we demonstrate that although TroR(Td) possessing various C-terminal deletions maintain metal-sensing capacities, these truncated proteins exhibit reduced repressor activities in comparison with full-length TroR(Td).Based upon these findings, we propose that TroR(Td) represents a novel member of the DtxR family of transcriptional regulators and is likely to play an important role in regulating both manganese and iron homeostases in this spirochaete.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA.

ABSTRACT
Treponema denticola harbours a genetic locus with significant homology to most of the previously characterized Treponema pallidum tro operon. Within this locus are five genes (troABCDR) encoding for the components of an ATP-binding cassette cation-transport system (troABCD) and a DtxR-like transcriptional regulator (troR). In addition, a sigma(70)-like promoter and an 18 bp region of dyad symmetry were identified upstream of the troA start codon. This putative operator sequence demonstrated similarity to the T. pallidum TroR (TroR(Tp)) binding sequence; however, the position of this motif with respect to the predicted tro promoters differed. Interestingly, unlike the T. pallidum orthologue, T. denticola TroR (TroR(Td)) possesses a C-terminal Src homology 3-like domain commonly associated with DtxR family members. In the present study, we show that TroR(Td) is a manganese- and iron-dependent transcriptional repressor using Escherichia coli reporter constructs and in T. denticola. In addition, we demonstrate that although TroR(Td) possessing various C-terminal deletions maintain metal-sensing capacities, these truncated proteins exhibit reduced repressor activities in comparison with full-length TroR(Td). Based upon these findings, we propose that TroR(Td) represents a novel member of the DtxR family of transcriptional regulators and is likely to play an important role in regulating both manganese and iron homeostases in this spirochaete.

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Primary sequence alignment of B. subtilis MntR (Bs MntR), C. diptheriae DtxR (Cd DtxR) and the T. pallidum (Tp) and T. denticola (Td) TroR proteins. The secondary structure of DtxR family metalloregulators is indicated above the sequence alignments: α-helices (α1, 2, 4, 5, 6) are shown in black, the DNA recognition helix (α3) is shown as a hatched line, β-strands (β1–2) are shown in grey and the proline-containing tether region (α7) is shown in black. The black boxes outline conserved metal co-ordination site residues in Bs MntR or Cd DtxR sequences. Putative TroR metal co-ordination site residues are highlighted in grey.
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fig02: Primary sequence alignment of B. subtilis MntR (Bs MntR), C. diptheriae DtxR (Cd DtxR) and the T. pallidum (Tp) and T. denticola (Td) TroR proteins. The secondary structure of DtxR family metalloregulators is indicated above the sequence alignments: α-helices (α1, 2, 4, 5, 6) are shown in black, the DNA recognition helix (α3) is shown as a hatched line, β-strands (β1–2) are shown in grey and the proline-containing tether region (α7) is shown in black. The black boxes outline conserved metal co-ordination site residues in Bs MntR or Cd DtxR sequences. Putative TroR metal co-ordination site residues are highlighted in grey.

Mentions: TroRTd is predicted to be a metal-dependent transcriptional regulator based on homology to the DtxR family of metalloregulators. This group of transcriptional regulators contain several Fe-activated repressor proteins, including Corynebacterium diptheriae DtxR, Mycobacterium tuberculosis IdeR and Streptomyces spp.; DesR, the Mn2+-activated regulators TroRTp and Bacillus subtilis MntR; and the Fe- and Mn2+-activated repressors Staphylococcus epidermidis SirR and Group A Streptococcus MtsR (Hill et al., 1998; Bates et al., 2005; Pennella and Giedroc, 2005). An alignment of the primary amino acid sequences of TroRTd with TroRTp, DtxR (Cd DtxR) and MntR (Bs MntR) is shown in Fig. 2. In general, Fe-responsive repressors have N-terminal domains (∼126 amino acids) containing helix–turn–helix DNA binding motifs (α2α3) and two metal ion binding sites (D'Aquino and Ringe, 2003). A short proline-containing region (∼26 amino acids) links this domain to the C-terminal region (∼76 amino acids) (Brennan and Matthews, 1989; Qiu et al., 1995; Schiering et al., 1995; D'Aquino and Ringe, 2003). TroRTd is predicted to have secondary structure similar to DtxR and to contain a comparable N-terminal DNA-binding domain followed by a helical dimerization domain. Additionally, similar to DtxR, TroRTd appears to possess an extended C-terminal Src homology 3-like (SH3-like) domain that is absent from TroRTp and MntR.


Treponema denticola TroR is a manganese- and iron-dependent transcriptional repressor.

Brett PJ, Burtnick MN, Fenno JC, Gherardini FC - Mol. Microbiol. (2008)

Primary sequence alignment of B. subtilis MntR (Bs MntR), C. diptheriae DtxR (Cd DtxR) and the T. pallidum (Tp) and T. denticola (Td) TroR proteins. The secondary structure of DtxR family metalloregulators is indicated above the sequence alignments: α-helices (α1, 2, 4, 5, 6) are shown in black, the DNA recognition helix (α3) is shown as a hatched line, β-strands (β1–2) are shown in grey and the proline-containing tether region (α7) is shown in black. The black boxes outline conserved metal co-ordination site residues in Bs MntR or Cd DtxR sequences. Putative TroR metal co-ordination site residues are highlighted in grey.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2628430&req=5

fig02: Primary sequence alignment of B. subtilis MntR (Bs MntR), C. diptheriae DtxR (Cd DtxR) and the T. pallidum (Tp) and T. denticola (Td) TroR proteins. The secondary structure of DtxR family metalloregulators is indicated above the sequence alignments: α-helices (α1, 2, 4, 5, 6) are shown in black, the DNA recognition helix (α3) is shown as a hatched line, β-strands (β1–2) are shown in grey and the proline-containing tether region (α7) is shown in black. The black boxes outline conserved metal co-ordination site residues in Bs MntR or Cd DtxR sequences. Putative TroR metal co-ordination site residues are highlighted in grey.
Mentions: TroRTd is predicted to be a metal-dependent transcriptional regulator based on homology to the DtxR family of metalloregulators. This group of transcriptional regulators contain several Fe-activated repressor proteins, including Corynebacterium diptheriae DtxR, Mycobacterium tuberculosis IdeR and Streptomyces spp.; DesR, the Mn2+-activated regulators TroRTp and Bacillus subtilis MntR; and the Fe- and Mn2+-activated repressors Staphylococcus epidermidis SirR and Group A Streptococcus MtsR (Hill et al., 1998; Bates et al., 2005; Pennella and Giedroc, 2005). An alignment of the primary amino acid sequences of TroRTd with TroRTp, DtxR (Cd DtxR) and MntR (Bs MntR) is shown in Fig. 2. In general, Fe-responsive repressors have N-terminal domains (∼126 amino acids) containing helix–turn–helix DNA binding motifs (α2α3) and two metal ion binding sites (D'Aquino and Ringe, 2003). A short proline-containing region (∼26 amino acids) links this domain to the C-terminal region (∼76 amino acids) (Brennan and Matthews, 1989; Qiu et al., 1995; Schiering et al., 1995; D'Aquino and Ringe, 2003). TroRTd is predicted to have secondary structure similar to DtxR and to contain a comparable N-terminal DNA-binding domain followed by a helical dimerization domain. Additionally, similar to DtxR, TroRTd appears to possess an extended C-terminal Src homology 3-like (SH3-like) domain that is absent from TroRTp and MntR.

Bottom Line: Interestingly, unlike the T. pallidum orthologue, T. denticola TroR (TroR(Td)) possesses a C-terminal Src homology 3-like domain commonly associated with DtxR family members.In addition, we demonstrate that although TroR(Td) possessing various C-terminal deletions maintain metal-sensing capacities, these truncated proteins exhibit reduced repressor activities in comparison with full-length TroR(Td).Based upon these findings, we propose that TroR(Td) represents a novel member of the DtxR family of transcriptional regulators and is likely to play an important role in regulating both manganese and iron homeostases in this spirochaete.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA.

ABSTRACT
Treponema denticola harbours a genetic locus with significant homology to most of the previously characterized Treponema pallidum tro operon. Within this locus are five genes (troABCDR) encoding for the components of an ATP-binding cassette cation-transport system (troABCD) and a DtxR-like transcriptional regulator (troR). In addition, a sigma(70)-like promoter and an 18 bp region of dyad symmetry were identified upstream of the troA start codon. This putative operator sequence demonstrated similarity to the T. pallidum TroR (TroR(Tp)) binding sequence; however, the position of this motif with respect to the predicted tro promoters differed. Interestingly, unlike the T. pallidum orthologue, T. denticola TroR (TroR(Td)) possesses a C-terminal Src homology 3-like domain commonly associated with DtxR family members. In the present study, we show that TroR(Td) is a manganese- and iron-dependent transcriptional repressor using Escherichia coli reporter constructs and in T. denticola. In addition, we demonstrate that although TroR(Td) possessing various C-terminal deletions maintain metal-sensing capacities, these truncated proteins exhibit reduced repressor activities in comparison with full-length TroR(Td). Based upon these findings, we propose that TroR(Td) represents a novel member of the DtxR family of transcriptional regulators and is likely to play an important role in regulating both manganese and iron homeostases in this spirochaete.

Show MeSH
Related in: MedlinePlus