Application): The long-range goal of this research proposal is to combine electrophysiological, biochemical, biophysical and molecular biological techniques to gain insight into the structure and function of the nicotinic acetylcholine receptor (AChR) with special attention on protein-lipid interactions. The emphasis of this project is organized on three independent approaches: (1) The first approach is to extend ongoing site directed mutagenesis at lipid-exposed residues of the Torpedo AChR that have shown to affect the channel gating mechanism. The investigators propose to introduce additional amino acid replacements at the new hydrophobic allosteric position alpha-V425 position. These studies will further test the hypothesis that a number of allosteric sites at the lipid protein interface have a critical role on the AChR channel gating. The identification and functional characterization of these lipid-exposed allosteric sites will provide further insights into the structure-function relationships of the AChR. (2) The second approach proposes to introduce periodic tryptophan substitutions to cover all the positions along the M4 transmembrane domains for beta, gamma and delta subunits. A systematic analysis of a series of tryptophan substitutions will provide information of the physical location of helix-helix or subunit-subunit contacts that are critical for the functional oligomerization of the AChR. The positional location of possible constraint sites may identify additional aspects of the spatial organization of the M4 transmembrane domains in respect to the Ml and M3 domains as well as to structure-function relationships of the AChR. (3) The third approach is to use novel Torpedo M4 AChR mutations to examine the sensitivity of the lipid-protein interface to the action of various types of general anesthetics. The objectives of this project are to define the biochemical and biophysical interactions of these allosteric sites and to identify additional aspects of the spatial organization of the M4 transmembrane domains of the AChR.
| Ramírez-Camejo, Luis A; Maldonado-Morales, Génesis; Bayman, Paul (2017) Differential Microbial Diversity in Drosophila melanogaster: Are Fruit Flies Potential Vectors of Opportunistic Pathogens? Int J Microbiol 2017:8526385 |
| Morales-Rivera, Keyla F; Piñero Cruz, Dalice M; Prieto, Jose A (2017) Crystal structure of (-)-(S)-4-[(2S,3S,4S,Z)-3-hydroxy-4-methyl-hept-5-en-2-yl]-1,3-dioxolan-2-one. Acta Crystallogr E Crystallogr Commun 73:1070-1072 |
| García-Arriaga, Marilyn; Acosta-Santiago, Maxier; Cruz, Antony et al. (2017) Probing the Limits of Supramolecular G-Quadruplexes Using Atomistic Molecular Dynamics Simulations. Inorganica Chim Acta 468:209-222 |
| Huang, Qing; Quiñones, Edwin (2016) A spectroscopic method to determine the activity of the restriction endonuclease EcoRV that involves a single reaction. Anal Biochem 497:103-5 |
| Mège, Pascal; Schizas, Nikolaos V; Reyes, Joselyd García et al. (2015) Genetic seascape of the threatened Caribbean elkhorn coral, Acropora palmata, on the Puerto Rico Shelf. Mar Ecol (Berl) 36:195-209 |
| Morales-Rivera, Amarilys; Hernández-Burgos, Mayté M; Martínez-Rivera, Arlene et al. (2014) Anxiolytic effects of oxytocin in cue-induced cocaine seeking behavior in rats. Psychopharmacology (Berl) 231:4145-55 |
| Ramírez-Camejo, Luis A; Torres-Ocampo, Ana P; Agosto-Rivera, José L et al. (2014) An opportunistic human pathogen on the fly: strains of Aspergillus flavus vary in virulence in Drosophila melanogaster. Med Mycol 52:211-9 |
| Martínez-Rivera, Arlene; Rodríguez-Borrero, Enrique; Matías-Alemán, María et al. (2013) Metabotropic glutamate receptor 5 within nucleus accumbens shell modulates environment-elicited cocaine conditioning expression. Pharmacol Biochem Behav 110:154-60 |
| Galindo-Cardona, Alberto; Acevedo-Gonzalez, Jenny P; Rivera-Marchand, Bert et al. (2013) Genetic structure of the gentle Africanized honey bee population (gAHB) in Puerto Rico. BMC Genet 14:65 |
| Santiago-Rodriguez, Tasha M; Rivera, Jessica I; Coradin, Mariel et al. (2013) Antibiotic-resistance and virulence genes in Enterococcus isolated from tropical recreational waters. J Water Health 11:387-96 |
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