Light is crucial for many essential biological processes such as photosynthesis, vision, circadian rhythms, etc., but can also cause photooxidative cellular damage. Living organisms sense and respond to light using photoreceptors, proteins associated with a light-sensing chromophoric cofactor such as retinal in the photoreceptors of the eye. In 2011, the research teams of Dr. S. Padmanabhan (NMR group, IQFR) and Prof. Montserrat Elías-Arnanz (Universidad of Murcia/Associated Unit to IQFR) discovered a novel photoreceptor family that uses vitamin B12 as the light-sensing molecule and revealed its mode of action in light-dependent gene regulation. These two teams, in collaboration with that of Prof. Catherine L. Drennan (Massachusetts Institute of Technology, USA), now report the crystal structures of the B12-dependent photoreceptor in all three relevant states: in the dark (both free and bound to DNA), and after light exposure; that is, three high-resolution snapshots that reveal the light-dependent conformational changes behind its mechanism of action. These findings expand the biological role assigned to vitamin B12, and enable a framework for the development of a new class of optogenetic tools for controlled gene expression.
Marco Jost, Jésus Fernández-Zapata, María Carmen Polanco, Juan Manuel Ortiz-Guerrero, Percival Yang-Ting Chen, Gyunghoon Kang, S. Padmanabhan, Montserrat Elías-Arnanz, and Catherine L. Drennan. “Structural basis for gene regulation by a B12-dependent photoreceptor” Nature 526, 536–541 (22 October 2015) DOI: 10.1038/nature14950 (Published online September 28, 2015).