The mechanism of a formaldehyde-sensing transcriptional regulator

• Published in: Scientific reports Vol. 6; no. 1; p. 38879
• Main Authors: Denby, Katie J., Iwig, Jeffrey, Bisson, Claudine, Westwood, Jodie, Rolfe, Matthew D., Sedelnikova, Svetlana E., Higgins, Khadine, Maroney, Michael J., Baker, Patrick J., Chivers, Peter T., Green, Jeffrey
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-12-2016; Nature Publishing Group
• Subjects: 101/58; 38/70; 631/45/535/1266; 631/45/612/822; 82; 82/83; 96/95; Amino Acid Sequence; Amino acids; Bacteria; Base Sequence; Chemistry; Crystallography, X-Ray; Derepression; Detoxification; DNA, Bacterial - genetics; DNA, Bacterial - metabolism; E coli; Escherichia coli K12 - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - physiology; Formaldehyde; Formaldehyde - metabolism; Formaldehyde - pharmacology; Gene Expression Regulation, Bacterial; Genotoxicity; Gram-positive bacteria; Humanities and Social Sciences; Inactivation, Metabolic; Interferometry; Models, Molecular; multidisciplinary; Operon; Promoter Regions, Genetic - genetics; Protein Conformation; Proteins; Repressor Proteins - chemistry; Repressor Proteins - genetics; Repressor Proteins - physiology; Salmonella; Science; Selenomethionine - chemistry; Sensors; Sequence Alignment; Sequence Homology, Amino Acid; Surface charge; Transcription; Transcription, Genetic
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep38879

Most organisms are exposed to the genotoxic chemical formaldehyde, either from endogenous or environmental sources. Therefore, biology has evolved systems to perceive and detoxify formaldehyde. The
frmRA(B)
operon that is present in many bacteria represents one such system. The FrmR protein is a transcriptional repressor that is specifically inactivated in the presence of formaldehyde, permitting expression of the formaldehyde detoxification machinery (FrmA and FrmB, when the latter is present). The X-ray structure of the formaldehyde-treated
Escherichia coli
FrmR (
Ec
FrmR) protein reveals the formation of methylene bridges that link adjacent Pro2 and Cys35 residues in the
Ec
FrmR tetramer. Methylene bridge formation has profound effects on the pattern of surface charge of
Ec
FrmR and combined with biochemical/biophysical data suggests a mechanistic model for formaldehyde-sensing and derepression of
frmRA(B)
expression in numerous bacterial species.