Molecular modeling and characterization of Vibrio cholerae transcription regulator HlyU.
BACKGROUND
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 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.


RESULTS
We 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.


CONCLUSIONS
The 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.
Saha
Rudra P
RP
Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Calcutta 700 054, India. rudra@bic.boseinst.ernet.in
Chakrabarti
Pinak
P
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D019281:Dimerization; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014734:Vibrio cholerae / Q000737:chemistry*
D001426:Bacterial Proteins; D021122:Protein Subunits; D014157:Transcription Factors; C084286:hlyU protein, Vibrio cholerae