Research
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Glycoproteins gp120 and gp41 are part of the AIDS HIV virus envelope. These proteins are involved in both, virus / host cell membrane fusion, a step essential for viral infection, and in the immune response to the virus. The knowledge of the structure of these proteins is crucial to understand these mechanisms at molecular level.
Scientists from the NMR group at the Institute of Physical-Chemistry ‘Rocasolano’ (CSIC), in collaboration with Dr. J. L. Nieva (University of the Basque Country) and Dr. J.M.M. Caaveiro (University of Tokyo) have determined the structure of several peptides reproducing sequences of the MPER (membrane-proximal external region) and TM (trans-membrane) sub-domains of the HIV gp41 protein. This work shows that the structure of the trans-membrane region, which has not been solved previously, presents two helices connected by a flexible segment. In addition, it has been found that the final MPER region and the initial TM region form a unique uninterrupted helix, in contrast to bioinformatics prediction. A model for the mechanism of virus / host cell membrane fusion has been proposed on the basis of these structural data. More interestingly, these data also explain the observed differences in antibody affinity, as well as the immune response of MPER-derived peptides. Accordingly, this information would be of great interest for a rational design of novel vaccines and inhibitors, useful as alternative therapies against AIDS.
The work has been selected as “Paper of the Week” by the editors of J. Biol. Chem.
Virion and envelope glycoprotein contour images were kindly provided by Dr. S. Subramaniam.
Reference:
B. Apellaniz, E. Rojas, S. Serrano, K. Morante, K. Tsumoto, J.M.M. Caaveiro, M.A. Jiménez, & J.L. Nieva. “The atomic structure of the HIV-1 gp41 MPER-TMD region reveals a continuously helical inter-domain connection flanked by two metastable hinge segments. Implications for MPER immunogenicity”. J. Biol. Chem. (2015). doi:10.1074/jbc.M115.644351.
Link to CSIC news
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The ability to resist the effect of a wide range of antibiotics makes methicillin-resistant Staphylococcus aureus (MRSA) a leading global human pathogen. A key determinant of resistance to -lactam antibiotics in this organism is penicillin-binding protein 2a (PBP2a), an enzyme that catalyzes the crosslinking reaction between two adjacent peptide stems during the peptidoglycan biosynthesis. In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2- (4-cyanostyryl)quinazolin-4(3H)-one as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional and structural assays showing binding of new antibiotic to PBP2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.
Reference:
Bouley, R.; Kumarasiri, M.; Peng, Z.; Otero, L.; Song, W.; Suckow, M.; Schroeder, V.; Wolter, W.; Lastochkin, E.; Antunes, N.; Pi, H.; Vakulenko, S.; Hermoso, J.; Chang, M.; Mobashery, S. Discovery of Antibiotic (E)-3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one, J. Am. Chem. Soc. 2015, 137, 1738-1741.
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Magnetite is the oldest magnetic material known to mankind. With applications in catalysis and magnetic storage of information, it has been proposed for use in spintronics. However, its surface magnetic properties are still under discussion. A basic property is the magnetic moment which on the surface may differ from its volumen value. However, the magnetic moment at surfaces and interfaces is crucial for its use in devices that manipulate the spin such as spin valves.
The first research work performed uniquely by means of the only low-energy electron and photoelectron microscope in Spain, located at the Alba synchrotron Alba, has just been published. The study, a collaboration between researchers from the Instituto de Química Física "Rocasolano" and the Alba synchrotron, has used the high surface sensitivity and multi-technique capabilities of the microscope to characterize the magnetic moment at the magnetite surface, finding that it is crucially affected by the local atomic structure.
Laura Martín-García, Raquel Gargallo-Caballero, Matteo Monti, Michael Foerster, José F. Marco, Lucía Aballe, and Juan de la Figuera, "Spin and orbital magnetic moment of reconstructed √2x√2R45º magnetite(001)", Phys. Rev. B (Rapid Comm) 91 (2015) 020408(R).
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Researchers at IQFR, in close collaboration with researchers from the Institute of Inorganic Chemistry of the Academy of Sciences of the Czech Republic, have demonstrated the existence of a new inorganic compound that emits laser light and that belongs to a kind of materials never considered before for such application; the boron hydrides or boranes. Specifically, the researchers have concentrated in their work on solutions of anti-B18H22, a polyhedral inorganic molecule containing 18 boron and 22 hydrogen atoms, with architecture resembling that of a split soccer ball joint at opposite edges.
With a quantum yield of fluorescence of 97%, this compound emits laser light at a wavelength of 400 nm, with an efficiency and photostability that is superior or similar to many of the commercially available state-of-the-art organic dyes in this spectral region. Such properties will enable, in a future to come, the reduction in the number of times the laser medium has to be replaced in the devices based in the use of solutions, helping to solve issues with costs, occupational hazards, and environmental impact due to handling of solvents, which are toxic, flammable, and even carcinogenic.
The scientific relevance of this discovery, which has been published in the journal Nature Communications, represents a milestone in the history of lasers, since there are not many occasions in which a new family of laser materials is unveiled.
L. Cerdán, J. Braborec, I. García-Moreno, A. Costela, M. G. S. Londesborough. A borane laser. Nature Communications (2015), DOI: 10.1038/ncomms6958
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Plants have to endure adverse environmental conditions, among them, drought and salinity constrain agricultural productivity most dramatically. Many of the plant adaptive responses take place at cell membrane where it is required the regulation o a variety of ion channels and transporters. This adjusts the intracellular ion concentration necessary for cell live. From a molecular point of view, the levels of abscisic acid (ABA) and calcium encode the information to orchestrate cell response to stress. We have discovered and characterized a new family of proteins, CAR for C2-domain ABA-related, that target ABA recognition machinery to the cell membrane. The joined structural and biochemical analyses has provided a working model that illustrates how CAR proteins anchor to plasma membrane and specifically bind the ABA receptors. As the activity of these proteins is dependent of calcium, they represent a central hub decoding ABA and calcium stimuli and provide a target for biotechnological work for the use of plants in our benefit.
C2-Domain Abscisic Acid-Related Proteins Mediate the Interaction of PYR/PYL/RCAR Abscisic Acid Receptors with the Plasma Membrane and Regulate Abscisic Acid Sensitivity in Arabidopsis
L. Rodriguez, M. Gonzalez-Guzmán, M. Díaz, A. Rodrigues, A.C. Izquierdo-Garcia, M. Peirats-Llobet, R. Antonia, D. Fernández, J.A. Márquez, J.M. Mulet, A. Albert and P.L. Rodríguez
The Plant Cell (2014) Advanced Online Publication (doi:10.1105/tpc.114.129973)
