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.

Descárgate este artículo aquí.
Más artículos en la revista SEBBM.

Did you publish an interesting article recently?

Send it through our application form and we will contact you. Age limit: 32.

The selected articles will participate at the Award to the best article of young people of the SEBBM which will be given during SEBBM conference, that will take place at Spain (free registration, travel and accommodation).

More articles of the month

ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements

01-05-2019

/Bacillus subtilis/ ParB forms multimeric networks involving non-specific DNA binding leading to DNA condensation. Previously, we found that an excess of the free C-terminal domain (CTD) of ParB impeded DNA...

Read more

Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer

01-04-2019

Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New...

Read more

p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton

01-03-2019

Planar cell polarity (PCP) and intercellular junctional complexes establish tissue structure and coordinated behaviors across epithelial sheets. In multiciliated ependymal cells, rotational and translational PCP coordinate cilia beating and direct...

Read more

β‐RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice

01-02-2019

Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In...

Read more

Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons

02-01-2019

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, a process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark is the accumulation of...

Read more

Dynamic acetylation of cytosolic phosphoenolpyruvate carboxykinase toggles enzyme activity between gluconeogenic and anaplerotic reactions

01-12-2018

Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is considered a gluconeogenic enzyme; however, its metabolic functions and regulatory mechanisms beyond gluconeogenesis are poorly understood. Here, we describe that dynamic acetylation of PCK1 interconverts...

Read more

The Helicase PIF1 Facilitates Resection overSequences Prone to Forming G4 Structures

02-11-2018

DNA breaks are complex lesions that can be repaired either by non-homologous end joining (NHEJ) or by homologous recombination (HR). The decision between these two routes of DNA repair is...

Read more

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation

01-10-2018

The nuclear membrane acts as a mechanosensor that drives cellular responses following changes in the extracellular environment. Mechanically ventilated lungs are exposed to an abnormally high mechanical load that may...

Read more

Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria

03-09-2018

Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear...

Read more

STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis

01-08-2018

The brain microenvironment imposes a particularly intense selective pressure on metastasis-initiating cells, but successful metastases bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of...

Read more

Protector Members