title: Protein signatures that promote operator selectivity among paralog MerR monovalent metal ion regulators.
abstract: Two paralog transcriptional regulators of the MerR family, CueR and GolS, are responsible for monovalent metal ion sensing and resistance in Salmonella enterica. Although similar in sequence and also in their target binding sites, these proteins differ in signal detection and in the set of target genes they control. Recently, we demonstrated that selective promoter recognition depends on the presence of specific bases located at positions 3' and 3 within the operators they interact with. Here, we identify the amino acid residues within the N-terminal DNA-binding domain of these sensor proteins that are directly involved in operator discrimination. We demonstrate that a methionine residue at position 16 of GolS, absolutely conserved among GolS-like proteins but absent in all CueR-like xenologs, is the key to selectively recognize operators that harbor the distinctive GolS-operator signature, whereas the residue at position 19 finely tunes the regulator/operator interaction. Furthermore, swapping these residues switches the set of genes recognized by these transcription factors. These results indicate that co-evolution of a regulator and its cognate operators within the bacterial cell provides the conditions to avoid cross-recognition and guarantees the proper response to metal injury.
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), Universidad Nacional de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Ocampo y Esmeralda, 2000-Rosario, Argentina.
authors.forename: María V
authors.initials: MV
authors.lastname: Humbert
authors.forename: Rodolfo M
authors.initials: RM
authors.lastname: Rasia
authors.forename: Susana K
authors.initials: SK
authors.lastname: Checa
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Soncini
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002414:Cations, Monovalent / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D008715:Methionine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019779:Salmonella enterica / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D001426:Bacterial Proteins; D002414:Cations, Monovalent; D004268:DNA-Binding Proteins; C051124:MerR protein, Bacteria; D008670:Metals; D009841:Oligonucleotides; D008715:Methionine
keywords: Bacterial Signal Transduction; Copper; DNA Operators; Helix-Loop-Helix Transcription Factors; MerR Regulators; Metal Homeostasis; Microbiology; Operator Selectivity; Prokaryotic Signal Transduction; Protein-DNA Interaction