Research

Details: Category: Research

imagen-lytb

Streptococcus pneumoniae (the pneumococus), a superbug bacteria, is a leading cause of bacterial sepsis and the most frequent ethiologic-agent in the community adquired pneumoniae and non-epidemic bacterial meningitis. LytB, a member of the family of pneumococcal choline-binding protein, is responsible for the physical separation of daugther cells after division and participates in nasopharinx colonization and invasion, biofilm formation and evasion from the host immunity. Because of this, LytB is considered a putative vaccine/drug target. Here, IQFR and CIB investigators, in collaboration with scientists from the Universities of Newcastle (Newcastle upon Tyne, UK) and Notre Dame (Indiana, USA), have shown that LytB is a glucosaminidase and the basis for its high substrate specificity are unveiled. The catalytic mechanism and model of binding to the bacterial peptidoglycan together with determinants of its polar localization on pneumococcal cells is also advanced. Reported data provide a better understanding of the complex physiological role played by LytB in the bacterium and the host-pathogen interaction.

Rico-Lastres P, Díez-Martínez R, Iglesias-Bexiga M, Bustamante N, Aldridge C, Hesek D, Lee M, Mobashery S, Gray J, Vollmer W, García P, Menéndez M. 2015. “Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence”. Sci Rep. 5:16198. doi: 10.1038/srep16198.

Details: Category: Research

foto-NASA-en

Bromine is an effective ozone destruction catalyst in the stratosphere, the region of the atmosphere that contains the ozone layer. Most bromine reaching the stratosphere comes from anthropogenic sources, which are controlled by the Montreal Protocol (an international treaty designed to protect the ozone layer of the Earth). In addition, an uncertain amount of natural organic bromine compounds, emitted from the oceans as a result of the marine biological activity, can reach the stratosphere where it contributes to the destruction of the ozone layer. In this work, these ocean-emitted organic bromine compounds have been measured for the first time both over the East and West Pacific Ocean in profiles from the ocean surface up to the gateway of the stratosphere, at 18 km. The measurements were made aboard the NASA´s non-tripulated Global Hawk aircraft as part of the NASA´s Airborne Tropical Tropopause Experiment (ATTREX) campaigns. This study also uses a climate model to quantify the impact of the injected natural bromine on the destruction of the ozone layer.

Maria A. Navarro, Elliot L. Atlas, Alfonso Saiz-Lopez, Xavier Rodriguez-Lloveras, Douglas E. Kinnison, Jean-Francois Lamarque, Simone Tilmes, Michal Filus, Neil R. P. Harris, Elena Meneguz, Matthew J. Ashfold, Alistair J. Manning, Carlos A. Cuevas, Sue M. Schauffler, and Valeria Donets. Airborne measurements of organic bromine compounds in the Pacific tropical tropopause layer. PNAS.
DOI: 10.1073/pnas.1511463112

Details: Category: Research

nature-2015-def

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).

Details: Category: Research

cover-art

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.

Details: Category: Research

ParaBioF-small

Only 2% of the genome codes for proteins. What does the rest do? What is its structure? One of the most intriguing and unknown regions in the eukaryotic genome is the centromere. IQFR and CMBSO researchers have recently shown that centromeric sequences of organisms as distant in the evolutionary tree as fruit flies and humans are able to fold in vitro forming the same type of secondary structure, known as the “i-motif”. The presence of these structures in such distant organisms suggests that they may be involved in the structural organization of the centromere. If this were the case, the centromeric DNA could have been selected during evolution not for its primary sequence, but for its capability to form this non-canonical structure, the “i-motif”.

This work is the result of a collaboration with our colleague and friend Alfredo Villasante, to whose memory it is dedicated.

M. Garavís, N. Escaja, V. Gabelica, A. Villasante and C. González. Centromeric alpha-satellite DNA adopts dimeric i-motif structures capped by AT Hoogsteen base pairs. Chemistry-A Eur. J., 21, 9816-9824, 2015. doi: 10.1002/chem.201500448 (artículo del mes SBE, junio 2015)

M. Garavís, M. Méndez-Lago, V. Gabelica, S. L. Whitehead G. González, and A. Villasante. The structure of an endogenous Drosophila centromere reveals the prevalence of tandemly repeated sequences able to form i-motifs. Sci. Rep., 5, 13307, 2015. doi: 10.1038/srep13307