title: The mechanism of a formaldehyde-sensing transcriptional regulator.
abstract: 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 (EcFrmR) protein reveals the formation of methylene bridges that link adjacent Pro2 and Cys35 residues in the EcFrmR tetramer. Methylene bridge formation has profound effects on the pattern of surface charge of EcFrmR and combined with biochemical/biophysical data suggests a mechanistic model for formaldehyde-sensing and derepression of frmRA(B) expression in numerous bacterial species.
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Denby
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Iwig
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK.
authors.forename: Claudine
authors.initials: C
authors.lastname: Bisson
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK.
authors.forename: Jodie
authors.initials: J
authors.lastname: Westwood
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Rolfe
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK.
authors.forename: Svetlana E
authors.initials: SE
authors.lastname: Sedelnikova
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, Amherst, MA 01003, USA.
authors.forename: Khadine
authors.initials: K
authors.lastname: Higgins
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, Amherst, MA 01003, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Maroney
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Baker
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.|Departments of Biosciences and Chemistry, Durham University, Durham, DH1 3LE, UK.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Chivers
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, S10 2TN, UK.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Green
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D048168:Escherichia coli K12 / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005557:Formaldehyde / Q000378:metabolism* / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D008658:Inactivation, Metabolic; D007368:Interferometry; D008958:Models, Molecular; D009876:Operon; D011401:Promoter Regions, Genetic / Q000235:genetics; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012645:Selenomethionine / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C000627585:FrmR protein, E coli; D012097:Repressor Proteins; D005557:Formaldehyde; D012645:Selenomethionine