Récepteurs olfactifs, modélisation et psychophysique... vers la compréhension du codage qualitatif des odeurs

National audienc

Les récepteurs des molécules odorantes et le codage olfactif

International audienc

Les récepteurs des molécules odorantes et le codage olfactif

International audienc

In vivo DNA electrotransfer in skeletal muscle

Appropriate electric pulses can reversibly permeabilize living cells both in vitro and in vivo. Since the pioneering work of E. Neumann and colleagues (1), cell electroporation (also often termed cell electropermeabilization) has become the most frequent method for cell transfection. Indeed, it easily applies in vitro to bacteria, yeast, animal, and plant cells. In vivo, the use of the DNA electrotransfer method is rapidly expanding because of its simplicity and efficiency. First attempts to transfer DNA in vivo to muscle cells were published in 1998 (2,3). This led in 1999 to an extended study on the determination of optimal conditions for DNA electrotransfer in skeletal muscle in mice, rats, rabbits, and even primates using a reporter gene (4). The same year, the first “therapeutic” gene (the erythropoïetin gene) was transferred to mouse muscle in vivo by Rizzuto and colleagues (5). In the last 2 years, several publications have used the conditions described in ref. (4) and have shown the wide applicability of this method for the electrotransfer of a large number of genes in different muscles (6-8). DNA electrotransfer to skeletal muscle could lead to broad potential applications in the therapeutic field (metabolic disorders correction, vaccination, systemic secretion of angiogenic or antiangiogenic factors, etc.) and for physiological, pharmacological, and developmental studiesVytauto Didžiojo universiteta

GPCRautomodel : outil de modélisation automatique de la structure 3D de récepteurs olfactifs de mammifères

Année de la première version : 2012Interface utilisateur : application WebMode de diffusion : service en lign

Automatic modeling of mammalian olfactory receptors and docking of odorants

We present a procedure that (i) automates the homology modeling of mammalian olfactory receptors (ORs) based on the first six three-dimensional (3D) structures of G protein- coupled receptors (GPCRs) available and (ii) performs the docking of odorants on these models, using the concept of colony energy to score the complexes. ORs exhibit low-sequence similarities with other GPCRs and current alignment methods often fail to provide a reliable alignment. Here, we use a fold recognition technique to obtain a robust initial alignment. The procedure is then applied to a human OR we had previously functionally characterized. The results, supported by receptor mutagenesis and functional assays, suggest that antagonists dock in the upper part of the binding pocket whereas agonists dock in the narrow lower part. We propose that the potency of agonists in activating receptors depends on their ability to establish tight interactions with the floor of the binding pocket. We developed a web site that allows the user to upload a GPCR sequence, choose a ligand in a library and obtain the 3D structure of the free receptor and ligand receptor complex (http://genome.jouy.inra.fr/GPCRautomodel)

3D-QSAR study of ligands for a human olfactory receptor

International audienc

3D-quantitative structure-activity relationships study of ligands for two human olfactory receptors

International audienceThe perception of thousands of odours by about 380 human olfactory receptors (ORs) results from a combinatorial coding, in which one OR recognizes multiple odorants and odorants are recognized by different combinations of ORs. We used data of 95 odorant molecules tested on two human ORs, OR1G1 (class II) and OR52D1 (class I), to perform a 3D molecular modelling study of ligands using Catalyst/HypoGen software. The sorting-out procedure previously used for OR1G1 ligands was transposed to OR52D1 ligands. The 3D-QSAR models obtained for OR1G1 and OR52D1 ligands essentially differ by distance between their features. This result suggests a path to decipher the odotopes of OR1G1 and OR52D1 agonists in order to investigate the role of ORs in olfactory coding

Olfactory receptor structure prediction and classification of ligand-receptor affinities

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