title: Light-dependent gene regulation by a coenzyme B12-based photoreceptor.
abstract: Cobalamin (B(12)) typically functions as an enzyme cofactor but can also regulate gene expression via RNA-based riboswitches. B(12)-directed gene regulatory mechanisms via protein factors have, however, remained elusive. Recently, we reported down-regulation of a light-inducible promoter in the bacterium Myxococcus xanthus by two paralogous transcriptional repressors, of which one, CarH, but not the other, CarA, absolutely requires B(12) for activity even though both have a canonical B(12)-binding motif. Unanswered were what underlies this striking difference, what is the specific cobalamin used, and how it acts. Here, we show that coenzyme B(12) (5'-deoxyadenosylcobalamin, AdoB(12)), specifically dictates CarH function in the dark and on exposure to light. In the dark, AdoB(12)-binding to the autonomous domain containing the B(12)-binding motif foments repressor oligomerization, enhances operator binding, and blocks transcription. Light, at various wavelengths at which AdoB(12) absorbs, dismantles active repressor oligomers by photolysing the bound AdoB(12) and weakens repressor-operator binding to allow transcription. By contrast, AdoB(12) alters neither CarA oligomerization nor operator binding, thus accounting for its B(12)-independent activity. Our findings unveil a functional facet of AdoB(12) whereby it serves as the chromophore of a unique photoreceptor protein class acting in light-dependent gene regulation. The prevalence of similar proteins of unknown function in microbial genomes suggests that this distinct B(12)-based molecular mechanism for photoregulation may be widespread in bacteria.
authors.affiliation: Department of Genetics and Microbiology, Area of Genetics, Unidad Asociada al Instituto de Química Física-Consejo Superior de Investigaciones Científicas, Faculty of Biology, Universidad de Murcia, Murcia 30100, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Ortiz-Guerrero
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Polanco
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Murillo
authors.forename: S
authors.initials: S
authors.lastname: Padmanabhan
authors.forename: Montserrat
authors.initials: M
authors.lastname: Elías-Arnanz
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002850:Chromatography, Gel; D003038:Cobamides / Q000378:metabolism*; D019295:Computational Biology; D024202:Electrophoretic Mobility Shift Assay; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D008027:Light; D008969:Molecular Sequence Data; D016941:Myxococcus xanthus / Q000378:metabolism*; D020283:Photoreceptors, Microbial / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013045:Species Specificity; D020798:Two-Hybrid System Techniques
chemical_list: D003038:Cobamides; D020283:Photoreceptors, Microbial; D012097:Repressor Proteins; C000913:cobamamide