Referencia

Proc Natl Acad Sci U S A. 2011 May 3;108(18):7565-7570. Epub 2011 Apr 18.

Autores

Juan Manuel Ortiz-Guerrero, María Carmen Polanco, Francisco J. Murillo, S. Padmanabhan, y Montserrat Elías-Arnanz

Resumen

Cobalamin (B12) typically functions as an enzyme cofactor but can also regulate gene expression via RNA-based riboswitches. B12-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 B12 for activity even though both have a canonical B12-binding motif. Unanswered were what underlies this striking difference, what is the specific cobalamin used, and how it acts. Here, we show that coenzyme B12 (5′-deoxyadenosylcobalamin, AdoB12), specifically dictates CarH function in the dark and on exposure to light. In the dark, AdoB12-binding to the autonomous domain containing the B12-binding motif foments repressor oligomerization, enhances operator binding, and blocks transcription. Light, at various wavelengths at which AdoB12 absorbs, dismantles active repressor oligomers by photolysing the bound AdoB12 and weakens repressor–operator binding to allow transcription. By contrast, AdoB12 alters neither CarA oligomerization nor operator binding, thus accounting for its B12-independent activity. Our findings unveil a functional facet of AdoB12 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 B12-based molecular mechanism for photoregulation may be widespread in bacteria.

Descripción

Los seres vivos responden a la luz, un agente ambiental clave en múltiples procesos biológicos, mediante el uso de fotorreceptores (proteínas que se asocian a ciertos compuestos fotosensibles denominados cromóforos, tales como el retinal en los fotorreceptores de los ojos). La naturaleza utiliza un número muy limitado de cromóforos. En este estudio se ha descubierto una nueva familia de proteínas fotorreceptoras que explotan la fotosensibilidad intrínseca de la vitamina B12 para responder a la luz, regulando la expresión génica. La vitamina B12, mejor conocida como cofactor de enzimas, es esencial para los seres humanos y otros animales, y su ausencia causa la anemia perniciosa. El estudio revela una nueva faceta funcional de la vitamina B12: la de formar parte de la selecta lista de compuestos cromóforos responsables de que ciertas proteínas tengan la capacidad de percibir la luz. El hallazgo podría servir también para la ingeniería de nuevas proteínas sintéticas diseñadas para realizar funciones biológicas específicas en respuesta a la luz.

Imágen artículo Junio

Arriba (de izqda. a dcha): Francisco García Heras, Antonio Angel Iniesta Martínez, Javier Abellón Ruiz, José Antonio Madrid, Juan Manuel Ortiz-Guerrero, S. Padmanabhan. Abajo (de izqda. a dcha): Montserrat Elías Arnanz, María Luisa Galbis Martínez, Francisco J. Murillo, María Carmen Polanco, Aranzazu Gallego García.

REFERENCIA DEL GRUPO E INVESTIGADOR
El grupo de Genética Molecular de la Universidad de Murcia, fundado por el Prof. Francisco Murillo Araujo y dirigido actualmente por la Prof. Montserrat Elías Arnanz, ha venido estudiando diversos fenómenos biológicos al nivel genético y molecular en la bacteria Myxococcus xanthus, centrándose sobre todo en la respuesta a la luz. Ha identificado la gran mayoría de los genes conocidos implicados en dicha respuesta y ha desentrañado el modo de acción molecular de varios de los componentes del sistema. Juan Manuel Ortiz-Guerrero es becario predoctoral y la Dra. María Carmen Polanco es Profesora Asociada en la Universidad de Murcia. El Dr. S. Padmanabhan es Investigador Científico y miembro del “Grupo de estructura, dinámica e interacciones de proteínas por RMN” en el Instituto de Química-Física “Rocasolano” del CSIC.

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