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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).
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Vitamin B12 is an essential enzyme cofactor in humans and other animals. Lack of B12 causes pernicious anemia, neural dysfunction and other disorders. A new molecular function for this vitamin was discovered a few years ago (PNAS, Vol. 108, p 7565-7570, 2011) in a collaboration between Dr. S. Padmanabhan of the NMR group (IQFR) and the Molecular Genetics group of Prof. Montserrat Elías-Arnanz (Universidad of Murcia and Associated Unit to IQFR). It was shown that B12 displays a new role as a light-sensing molecule and that it is involved in light-dependent gene regulation. Now, these researchers in collaboration with others at the University of Manchester (UK), have published a detailed photochemical mechanism for this new class of photoreceptors. The work provides a mechanistic foundation for the emerging field of B12 photobiology and a basis for the development of this class of photoreceptors as optogenetic tools for controlled gene expression in cells and organisms.
Roger J. Kutta, Roger J. Kutta, Samantha J. O. Hardman, Linus O. Johannissen, Bruno Bellina, Hanan L. Messiha, Juan Manuel Ortiz-Guerrero, Montserrat Elías-Arnanz, S. Padmanabhan, Perdita Barran, Nigel S. Scrutton, Alex R. Jones. The photochemical mechanism of a B12-dependent photoreceptor protein. Nature Communications, 6,
Article number 7907, August 12, 2015. doi: 10.1038/ncomms8907.
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We all know someone who has undergone a Nuclear Magnetic Resonance (NMR) scan. But only very few know that NMR is a powerful tool for the determination of the three-dimensional structure of molecules. This has been explained by Dr. Marta Bruix, from the Protein Structure, Dynamics and Interactions by NMR Group, on April 20th in the RTVE program “On Giant's Shoulders” (http://bit.ly/1LbRKEk).
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A collaboration between the Institute of Physical-Chemistry “Rocasolano” (CSIC) and the Institute of Molecular Sciences from the University of Valencia has led to a chapter in the book “Boron: The fifth element” (Springer Verlag), within the series “Challenges and Advances in Computational Chemistry and Physics”. Since the disclosure of borane compounds - polyhedral BxHy structures - as rocket fuel in the 1950’s, the research in this field, particularly on the synthesis of boranes and their derivatives, has grown exponentially. This multi-author book reviews the recent developments in boron chemistry, with a particular emphasis on the contribution of computational chemistry.
Josep M. Oliva, Antonio Francés-Monerris, and Daniel Roca-Sanjuán, “Quantum Chemistry of Excited States in Polyhedral Boranes”. Capítulo 4 en “Boron: The Fifth Element”, volumen 20 de la serie “Challenges and Advances in Computational Chemistry and Physics”, Editorial Springer (2016) ISBN 978-3-319-22282-0.
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Ultrathin islands of up to 100 μm2 with atomically flat surfaces and free from antiphase boundaries are developed. The extremely low defect concentration leads to a robust magnetic order, even for thicknesses below 1 nm, and exceptionally large magnetic domains. This approach allows the evaluation of the influence of specific extrinsic effects on domain wall pinning. The work has been performed by researchers of the Instituto de Quimica-Física "Rocasolano" and other CSIC institutes (ICV, ICMM) in collaboration with Alba synchrotron scientists.
L. Martín-García, A. Quesada, C. Munuera, J.F. Fernández, M. García-Hernández, M. Foerster, L. Aballe, J. de la Figuera. Atomically flat ultrathin cobalt ferrite islands.Advanced Materials. DOI: 10.1002/adma.201502799
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Galactitol-1-phosphate 5-dehydrogenase (GPDH) is a polyol dehydrogenase that catalyses the Zn2+ and NAD+-dependent stereoselective dehydrogenation of L-galactitol-1-phosphate to D-tagatose-6-phosphate. J.M. Mancheño (Dept. of Crystallography) in collaboration with Gert W. Kohring, Federico Gago and Rosario Muñoz, have reported three crystal structures of GPDH from Escherichia coli: the open state with Zn2+ in the catalytic site and also those of the closed state in complex with the polyols Tris and glycerol, respectively, but with no cofactor bound, which contrast with the behaviour of the prototypical mammalian liver alcohol dehydrogenase. Unexpectedly, a large internal cavity was found at the main contacting interface between GPDH subunits (GPDH is a dimer) that probably facilitates their relative movement. The binding mode of the substrate analogue glycerol reveals, for the first time in the polyol dehydrogenases, a penta-coordinated zinc ion in complex with a polyol and also a strong hydrogen bond with the conserved Glu144, an interaction originally proposed more than thirty years ago that supports a catalytic role for this acidic residue.
Rocío Benavente, María Esteban-Torres, Gert-Wieland Kohring, Álvaro Cortés-Cabrera, Pedro A. Sánchez-Murcia, Federico Gago, Iván Acebrón, Blanca De Las Rivas, Rosario Muñoz, José M. Mancheño. “Enantioselective oxidation of galactitol-1-phosphate by galactitol-1-phosphate 5-dehydrogenase from Escherichia coli”. Acta Crystallographica (2015) D71, 1540-1554.
(doi: 10.1107/S1399004715009281)
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Amyotrophic Lateral Sclerosis (ALS) is a mortal neuromuscular disease that affects 2800 persons in Spain, with two new cases being diagnosed each day. Abnormal aggregates of the protein “TDP-43” (transactive response DNA binding protein 43 kDa) are found in >95% of dying motor neurons, and have been linked to other neurodegenerative disease, including Alzheimer’s disease and Frontotemporal Lobar Degeneration. Aggregation of TDP-43 was traced to a small, Asn- and Gln-rich region of the protein spanning residues 341-357, but the conformation of this segment and how it oligomerizes into harmful aggregates was unknown. Here, on the basis of multiple biochemical assays and biophysical experiments, IQFR investigators in collaboration with scientists from Columbia University (New York), the Cajal Institute (CSIC), IMDEA Nanoscience (CAM), and the International Centre for Genetic Engineering and Biotechnology (Trieste, IT) show that this segment’s beta hairpin motifs assemble into an amyloid-like structure with an unusual fibril morphology. Using computational methods, they have advanced an amyloid-like structural model for the aggregate in which TDP-43 (341-357) beta hairpins dock in a novel, parallel topology. This structural model will likely aid our understanding of TDP-43’s role in neurodegenerative diseases and may help guide the search for treatments.
M. Mompeán, R. Hervás, Y. Xu, T.H. Tran, C. Guarnaccia, E. Buratti, F. Baralle, L. Tong, M. Carrión-Vázquez, A.E. McDermott, D.V. Laurents
J. Phys. Chem. Letters, June 2015, doi: 10.1021/acs.jpclett.5b00918
