title: Structural basis for gene regulation by a B12-dependent photoreceptor.
abstract: Photoreceptor proteins enable organisms to sense and respond to light. The newly discovered CarH-type photoreceptors use a vitamin B12 derivative, adenosylcobalamin, as the light-sensing chromophore to mediate light-dependent gene regulation. Here we present crystal structures of Thermus thermophilus CarH in all three relevant states: in the dark, both free and bound to operator DNA, and after light exposure. These structures provide visualizations of how adenosylcobalamin mediates CarH tetramer formation in the dark, how this tetramer binds to the promoter -35 element to repress transcription, and how light exposure leads to a large-scale conformational change that activates transcription. In addition to the remarkable functional repurposing of adenosylcobalamin from an enzyme cofactor to a light sensor, we find that nature also repurposed two independent protein modules in assembling CarH. These results expand the biological role of vitamin B12 and provide fundamental insight into a new mode of light-dependent gene regulation.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Jost
authors.affiliation: Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain.
authors.forename: Jésus
authors.initials: J
authors.lastname: Fernández-Zapata
authors.affiliation: Department of Genetics and Microbiology, Area of Genetics (Unidad Asociada al Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas), Faculty of Biology, Universidad de Murcia, Murcia 30100, Spain.
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Polanco
authors.affiliation: Department of Genetics and Microbiology, Area of Genetics (Unidad Asociada al Instituto de Química Física "Rocasolano", 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.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Percival Yang-Ting
authors.initials: PY
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Gyunghoon
authors.initials: G
authors.lastname: Kang
authors.affiliation: Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Padmanabhan
authors.affiliation: Department of Genetics and Microbiology, Area of Genetics (Unidad Asociada al Instituto de Química Física "Rocasolano", Consejo Superior de Investigaciones Científicas), Faculty of Biology, Universidad de Murcia, Murcia 30100, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Elías-Arnanz
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.|Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.|Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Drennan
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D003038:Cobamides / Q000378:metabolism* / Q000528:radiation effects; D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D003624:Darkness; D019281:Dimerization; D015964:Gene Expression Regulation, Bacterial / Q000528:radiation effects; D008027:Light; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009875:Operator Regions, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D020836:Protein Structure, Quaternary / Q000528:radiation effects; D016963:Thermus thermophilus / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects; D014158:Transcription, Genetic / Q000235:genetics / Q000528:radiation effects; D014805:Vitamin B 12 / Q000378:metabolism* / Q000528:radiation effects
chemical_list: D001426:Bacterial Proteins; D003038:Cobamides; D004269:DNA, Bacterial; C000913:cobamamide; D014805:Vitamin B 12