Unraveling the activation mechanism of olfactory receptors. Towards the future of structure odor relationships

Unraveling the activation mechanism of olfactory receptors. Towards the future of structure odor relationships. 14. Weurman flavour research symposium

Bioinspired sensors from olfactory proteins

Interaction between odorants and proteins involved in the perception of smell: the case of odorant-binding proteins probed by molecular modelling and biophysical data

A joint approach that combines molecular modelling and fluorescence spectroscopy is used to study the affinity of an odorant binding protein towards various odorant molecules. We focus on the capability of molecular modelling to rank odorants according to their affinity with this protein, which is involved in the sense of smell. Although ligand-based approaches are unable to propose an accurate model attending to the strength of the bond with the odorant-binding protein, receptor-based structures considering either static or dynamic structure of the protein perform equally to discriminate between good, medium and low affinity odorants. Such approaches will be useful for further rational des…

Extracellular loop 2 of G protein-coupled olfactory receptors is critical for odorant recognition

International audience; G protein-coupled olfactory receptors (ORs) enable us to detect innumerous odorants. They are also ectopically expressed in non-olfactory tissues and emerging as attractive drug targets. ORs can be promiscuous or highly specific, which is part of a larger mechanism for odor discrimination. Here, we demonstrate that the OR extracellular loop 2 (ECL2) plays critical roles in OR promiscuity and specificity. Using site-directed mutagenesis and molecular modeling, we constructed 3D OR models in which ECL2 forms a lid over the orthosteric pocket. We demonstrate using molecular dynamics simulations that ECL2 controls the shape and the volume of the odorant-binding pocket, m…

Périréception et protéines porteuses

ISBN-10 : 978-2-7592-1770-0 ; issn : 1777-4624

Molecular dynamics simulations reveal the active and inactive states of olfactory receptors

Ces molécules qui éveillent nos papilles

The sense of taste is a chemical sense and one of the most ancestral sensory modalities. It allows detectingand appreciating taste molecules present in our food. Beyond our vital needs, the pleasure elicited from whatwe eat can drive our feeding behaviors sometimes up to excess. Food intake involves several sensorysystems, mainly smell and taste. The underlying molecular mechanisms are relatively complex. This articlefocuses on the extent of the chemical space associated with the five primary tastes (sour, salty, sweet, bitterand umami), and details the fundamental role of gustatory receptors in the perception of taste as well aswithin interindividual variabilities.

The human OR1G1 olfactory receptor is differentially activated by various sandalwood odorants. A joint approach combining in silico and in vitro experiments

International audience; Sandalwood is a highly valuable component in perfumery. The action mode of sandalwood odorant molecules remains to be addressed. In fact, olfactory receptors involved in their perception have not yet been identified. The interaction of a human olfactory receptor, hOR1G1, with sandalwood odorants has been investigated. By means of cellular biology and functional tests experiments, we provide an additional insight to our atomic model of OR1G1 and our olfactophore approach performed on various odorants. The studied odorants cover a wide range of structures and sandalwood intensities. We experimentally show that beta-santalol is a strong agonist of hOR1G1, contrarily to …

Towards computational biomimetic nose

International audience