Abstract
BackgroundThe SmtB/ArsR family of prokaryotic metal-regulatory transcriptional repressors represses the expression of operons linked to stress-inducing concentrations of heavy metal ions, while derepression results from direct binding of metal ions by these 'metal-sensor' proteins. The HlyU protein from Vibrio cholerae is the positive regulator of haemolysin gene, it also plays important role in the regulation of expression of the virulence genes. Despite the understanding of biochemical properties, its structure and relationship to other protein families remain unknown.ResultsWe find that HlyU exhibits structural features common to the SmtB/ArsR family of transcriptional repressors. Analysis of the modeled structure of HlyU reveals that it does not have the key metal-sensing residues which are unique to the SmtB/ArsR family of repressors, yet the tertiary structure is very similar to the family members. HlyU is the only member that has a positive control on transcription, while all the other members in the family are repressors. An evolutionary analysis with other SmtB/ArsR family members suggests that during evolution HlyU probably occurred by gene duplication and mutational events that led to the emergence of this protein from ancestral transcriptional repressor by the loss of the metal-binding sites.ConclusionThe study indicates that the same protein family can contain both the positive regulator of transcription and repressors – the exact function being controlled by the absence or the presence of metal-binding sites.
Highlights
The SmtB/ArsR family of prokaryotic metal-regulatory transcriptional repressors represses the expression of operons linked to stress-inducing concentrations of heavy metal ions, while derepression results from direct binding of metal ions by these 'metal-sensor' proteins
Significant similarities were found with several ArsR family of transcription regulators (Table 1) suggesting that Vibrio cholerae HlyU (Vc-HlyU) may belong to the same family
The proteins are CadC from Staphylococcus aureus pI258, CzrA from Staphylococcus aureus, and SmtB from Synechococcus sp., which could be considered as possible templates for modeling of Vc-HlyU using the threading approach, which allows to assess the compatibility of the target sequence with the available protein folds based on the sequence similarity and on structural considerations [17,18]
Summary
The SmtB/ArsR family of prokaryotic metal-regulatory transcriptional repressors represses the expression of operons linked to stress-inducing concentrations of heavy metal ions, while derepression results from direct binding of metal ions by these 'metal-sensor' proteins. The SmtB/ArsR family of metalloregulators is present in many bacteria and archaea, and its members respond to a variety of different metals Even in this wellstudied regulator family, the determinants conferring metal specificity are only beginning to be understood [1]. Members of this family possess a highly conserved DNA recognition helix-turn-helix (HTH) domain and bind as homodimers to their operator/promoter (O/P) sequences, repressing the expression of operons associated with metal ion sequestration or efflux in both Grampositive and Gram-negative bacteria, allowing these organisms to survive when challenged with toxic concentrations of heavy metal ions [2]. CmtR is a Pb(II)/Cd(II)-sensing SmtB/ArsR metalloregulatory repressor that lacks both typical α3N and α5 sites and possesses a novel metal-sensing site at the α4 or the DNA-recognition helix [11]
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