Characterization of rat glutathione transferases in olfactory epithelium and mucus

International audience; The olfactory epithelium is continuously exposed to exogenous chemicals, including odorants. During the past decade, the enzymes surrounding the olfactory receptors have been shown to make an important contribution to the process of olfaction. Mammalian xenobiotic metabolizing enzymes, such as cytochrome P450, esterases and glutathione transferases (GSTs), have been shown to participate in odorant clearance from the olfactory receptor environment, consequently contributing to the maintenance of sensitivity toward odorants. GSTs have previously been shown to be involved in numerous physiological processes, including detoxification, steroid hormone biosynthesis, and am…

Highly sensitive olfactory biosensors for the detection of volatile organic compounds by surface plasmon resonance imaging

International audience; Nowadays, monitoring of volatile organic compounds (VOCs) is very important in various domains. In this work, we aimed to develop sensitive olfactory biosensors using odorant binding proteins (OBPs) as sensing materials. Three rat OBP3 derivatives with customized binding properties were designed and immobilized on the same chip for the detection of VOCs in solution by surface plasmon resonance imaging (SPRi). We demonstrated that the proteins kept their binding properties after the immobilization under optimized conditions. The obtained olfactory biosensors exhibited very low limits of detection in both concentration (200pM of beta-ionone) and in molecular weight of …

Novel scaffold of natural compound eliciting sweet taste revealed by machine learning

Abstract Sugar replacement is still an active issue in the food industry. The use of structure-taste relationships remains one of the most rational strategy to expand the chemical space associated to sweet taste. A new machine learning model has been setup based on an update of the SweetenersDB and on open-source molecular features. It has been implemented on a freely accessible webserver. Cellular functional assays show that the sweet taste receptor is activated in vitro by a new scaffold of natural compounds identified by the in silico protocol. The newly identified sweetener belongs to the lignan chemical family and opens a new chemical space to explore.

[Fri-P2-105] Deciphering the ligand binding properties of the mouse odorant-binding protein OBP5 from Mus musculus

International audience; Odorant-binding proteins (OBPs) are abundant soluble proteins secreted in the nasal mucus of a variety of species which are believed to be involved in the transport of odorants towards olfactory receptors. In this study, we report the functional characterization of mouse OBP5 (mOBP5). mOBP5 was recombinantly expressed as a hexahistidine-tagged protein in bacteria and purified by metal affinity. Oligomeric state and secondary structure composition of mOBP5 was investigated using gel filtration and circular dichroism spectroscopy. Fluorescent experiments revealed that mOBP5 interacts with the fluorescent probe N-phenyl naphthylamine (NPN) with a micromolar affinity. Co…

Engineering the sweet-tasting protein brazzein: analysis the effects on stability and sensory profile

International audience

Dietary xenoestrogens differentially impair 3T3-L1 preadipocyte differentiation and persistently affect leptin synthesis

International audience; Recent observations have highlighted adipogenesis alterations under exposure to several xenoestrogens at critical stages, and pointed at their possible involvement in the pathogenesis of obesity. However, it remains unclear whether these effects are mediated by classical estrogen receptor (ER) binding and subsequent transcriptional modulation. The aim of this study was to determine the (anti-)adipogenic impact of apigenin, bisphenol A, genistein and 17β-estradiol at the onset of adipose cell maturation, and to correlate it to their estrogenic potential. In steroid-free conditions, 3T3-L1 preadipocytes were induced to differentiate in the presence of xenoestrogens for…

Engineering the full sequence space of the sweet-tasting protein brazzein

International audience

Sweeteners and sweetness enhancers

indexation en cours; PURPOSE OF REVIEW: The current review summarizes and discusses current knowledge on sweeteners and sweetness enhancers. RECENT FINDINGS: The perception of sweet taste is mediated by the type 1 taste receptor 2 (T1R2)/type 1 taste receptor 3 (T1R3) receptor, which is expressed in the oral cavity, where it provides input on the caloric and macronutrient contents of ingested food. This receptor recognizes all the compounds (natural or artificial) perceived as sweet by people. Sweeteners are highly chemically diverse including natural sugars, sugar alcohols, natural and synthetic sweeteners, and sweet-tasting proteins. This single receptor is also the target for developing …

Structure-based virtual screening of bitter taste receptors

Understanding how chemicals code for a certain type of taste is fundamental for the development of a rational method to create new taste modulators. The identification of these new candidates is important for the food industry and would also be beneficial for the pharmacology industry. In humans, the bitter taste depends on a large family of 25 taste receptors type 2 (TAS2Rs) belonging to the G protein-coupled receptor (GPCR) family. They are classified distantly related to class A GPCR and, to date, the experimental structures have not been determined for any TAS2Rs. Here we present a new structure-based virtual screening strategy to expand the chemical space of bitter taste receptors. Com…

Prediction of sweetness potency from sweet taste receptor dose-response curves

International audience

Perceptual responses to odorant mixtures originate mainly from peripheral processing

International audience

Development of novel biomimetic sensor materials for optoelectronic nose applications

International audience

Characterization of rat glutathione transferases in olfactory mucus and epithelium

International audience

Evidence for multiple interactions at the olfactory receptor level

International audience

Antimutagenic activity of organosulfur compounds from Allium is associated with phase II enzyme induction

In a previous study, we showed that naturally occurring organosulfur compounds (OSCs) from garlic and onion modulated the activation of carcinogen via the alteration of cytochromes P450. The present study was undertaken to determine the incidence of the in vivo induction of phase II enzymes by individual OSCs on the genotoxicity of several carcinogens. Diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered by gavage (1mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects of treatments on phase II enzymes and on the genotoxicity of carcinogens were evaluated with hepatic cytosols and microsomes from OSCs-treated…

Numerical models contribute to expand the sweet taste chemical space

Mechanisms of protection against aflotoxin B1 genotoxycity in rats treated by organosulfur compounds from garlic

International audience

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…

The membrane-associated MUC1 improves adhesion of salivary MUC5B on buccal cells. Application to development of an in vitro cellular model of oral epithelium

Objectives: The mucosal pellicle is a thin layer of salivary proteins, mostly MUC5B mucins, anchored to epithelial oral cells. This pellicle is involved in protection of oral mucosae against abrasion, pathogenic microorganisms or chemical xenobiotics. The present study aimed at studying the involvement of MUC1 in mucosal pellicle formation and more specifically in salivary MUC5B binding using a cell-based model of oral epithelium. DESIGN: MUC1 mRNAs were not detected in TR146 cells, and therefore a stable cell line named TR146/MUC1 expressing this protein was developed by transfection. TR146 and TR146/MUC1 were incubated with human saliva in order to evaluate retention of MUC5B by epithelia…

Plasmalogen depletion in Müller glia alters both Cx43 expression and gap junction intercellular communication with neighbouring astrocytes

International audience

The impact of transmembrane mucin and dietary tannins on the electric properties of the oral mucosal pellicle studied by Scanning Microwave Microscopy

Oral and extra-oral receptors: what roles?

La perception du goût est médiée par différents types de récepteurs impliqués dans la perception de chacune des cinq saveurs fondamentales à savoir le salé, le sucré, l’acide, l’amer et l’umami (perception de certains acides aminés tels que le L-glutamate). L’identification de ces différents récepteurs a notamment permis de mieux comprendre les mécanismes moléculaires sous-jacents à ces perceptions. Le nombre de récepteurs pour chacune des saveurs ainsi que l’affinité qu’ils présentent pour les molécules sapides sont directement corrélées à la fonction biologique qui sous-tendent la détection de ces molécules. Ainsi, par exemple les sucres naturels source d’énergie pour l’organisme sont dét…

Implication des enzymes dans la perception chimio-sensorielle : une piste dans les troubles olfacto-gustatifs induits par des xénobiotiques ?

International audience

Odorant-binding protein-based optoelectronic tongue and nose for sensing volatile organic compounds

International audience; We developed an array of odorant-binding protein mutants with various binding properties. The same design is suitable for the detection and identification of volatile organic compounds (VOCs) both in the liquid phase and in the gas phase by surface plasmon resonance imaging. The obtained optoelectronic tongue is highly selective at low concentrations of VOCs with a low detection limit, but a narrow linear range. In comparison, the optoelectronic nose gives a much higher signal to noise ratio, but the discrimination of VOCs from different chemical classes requires kinetic data to get rid of non-specific signals. This work shows that these optoelectronic tongue and nos…

Design of an in-vitro model of oral mucosa: microscopic characterization

International audience

Resolution of the X-ray structure of gurmarin: new insights into the molecular mechanism of sweet taste receptor inhibition

International audience

The bitter taste of vitamins is mediated by human TAS2R activation

Vitamins play an important role in maintaining normal physiologic and metabolic functions. Vitamins are known to generate bitterness, which may contribute to the off-taste of nutritional supplements. This negative sensation may decrease product acceptability and patient compliance. Few studies have examined taste thresholds and sensory sensing mechanisms at the origin of vitamin taste detection. To better understand vitamin bitterness perception, we combined human sensory analysis and taste receptor functional assays. We measured the aqueous taste detection threshold of four B vitamins using sensory difference tests. Challenging the 25 human bitter taste 2 receptors (TAS2Rs), we found that …

Expression and characterization of the human sweet taste receptor expressed in a mammalian inducible cell line

International audience; Sweet taste perception is mediated by a heterodimeric receptor composed of the two distinct protein subunits, TAS1R2 and TAS1R3. TAS1R2 and TAS1R3 subunits are members of the small family of class C GPCRs. Class C GPCRs share a large N-terminal domain (NTD) linked to the heptahelical transmembrane domain by a cysteine-rich region. TAS1R2/TAS1R3 is the primary receptor for a diverse range of sweet compounds including natural sugars, sweet amino acids, artificial sweeteners and plant sweet-tasting proteins. In order to understand the molecular mechanisms that govern receptor – ligand interactions and the relative contribution of the two subunits to the detection of swe…

Interactions at the olfactory receptor level contribute to the coding of odorant mixtures

International audience

Interactions between aroma compounds and the oral mucosa could be responsible for aroma persistence

Interactions between aroma compounds and the oral mucosa could be responsible for aroma persistence. 4. international conference on food oral processing - “Food Oral Processing through life: interplay between food structure, sensory, pleasure and nutritional needs.”

Biophysical and functional characterization of the human olfactory receptor OR1A1 expressed in a mammalian inducible cell line

International audience; Olfactory receptors (ORs) play a crucial role in detecting the odorant molecules present in the surrounding environment. These receptors, which belong to class A G-protein-coupled receptors, constitute the largest transmembrane protein family in the human genome. Functional studies showed that the OR family includes members that are able to respond to a large set of odorants and members that are activated by a relatively small number of related odorants. To understand the molecular mechanisms that govern the receptor-ligand interactions, we overexpressed the human OR hOR1A1 in a stable tetracycline-inducible HEK293S cell line. This receptor was engineered by insertin…

Identification de nouveaux antagonistes des récepteurs aux endocannabinoïdes à action périphérique susceptibles d'améliorer les paramètres glucido-lipidiques chez la souris obèse

Identification de nouveaux antagonistes des récepteurs aux endocannabinoïdes à action périphérique susceptibles d'améliorer les paramètres glucido-lipidiques chez la souris obèse. 30. réunion de l’association française d’étude et de recherche sur l’Obésite (AFERO)

Strategy for recombinant expression of soluble functional N-terminal domain of human sweet taste receptor produced in Escherichia coli

International audience

Could aroma compounds interact with the endocannabinoid system?

National audience

Development of a new in vitro model of oral mucosa to investigate a new hypothesis on the molecular origin of astringency

Astringency is described as an oral tactile perception occurring during the consumption of tannin-rich foods. This sensation, mediated by the trigeminal nerves, participates negatively to the flavor of foods leading to the rejection of food with high astringency by the consumer. The exact molecular mechanism of its origin and the nature of the sensory receptors activated are still under debate. Up to recently, the main hypotheses involved changes in the lubrication properties of the oral cavity triggering the activation of mechanoreceptors. Recently, we have put a new hypothesis involving the mucin MUC1 forward as an explanation of the origin of astringency. MUC1 is a transmembrane mucin wi…

Evidence of interactions between aroma compounds and the CB1 receptor opens new routes for regulation of food intake

Characterization of the ligands for the human umami taste receptor

National audience; Among our basics senses, taste and our gustatory system allow us to perceive and recognize essential chemical nutrients present in food. Human can detect and discriminate five basics taste (sweet, bitter, sour, salty and umami) and recent studies proposed a sixth taste for fat. The umami taste is described as a « savory » sensation elicited mainly by L-amino acids and is thought to serve as an indicator of protein rich foods and promote feeding.The umami taste receptor is a heterodimeric receptor composed of the T1R1 and T1R3 subunits. These subunits belong to the family class C G protein-coupled receptors (GPCRs) and are constituted by a large N-terminal domain (NTD) lin…

Expression and differential localization of xenobiotic transporters in the rat olfactory neuro-epithelium.

International audience; Transporters, such as multidrug resistance P-glycoproteins (MDR), multidrug resistance-related proteins (MRP) and organic anion transporters (OATs), are involved in xenobiotic metabolism, particularly the cellular uptake or efflux of xenobiotics (and endobiotics) or their metabolites. The olfactory epithelium is exposed to both inhaled xenobiotics and those coming from systemic circulation. This tissue has been described as a pathway for xenobiotics to the brain via olfactory perineural space. Thereby, olfactory transporters and xenobiotic metabolizing enzymes, dedicated to the inactivation and the elimination of xenobiotics, have been involved in the toxicological p…

The Crystal Structure of Gurmarin, a Sweet Taste–Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition

International audience; Gurmarin is a highly specific sweet-taste suppressing protein in rodents that is isolated from the Indian plant Gymnemasylvestre. Gurmarin consists of 35 amino acid residues containing three intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.45 Å resolution and compare it with previously reported NMR solution structures. The atomic structure at this resolution allowed us to identify a very flexible region consisting of hydrophobic residues. Some of these amino acid residues had been identified as a putative binding site for the rat sweet taste receptor in a previous study. By combining alanine-scanning …

Development of a novel olfactory biosensor based on surface plasmon resonance imaging

Monitoring volatile organic compounds (VOCs) is a key issue in many industrial domains, from food industry to public safety. Here, we propose a biomimetic alternative to traditional analytical methods such as gas chromatography and mass spectroscopy. Novel olfactory biosensor was developed using surface plasmon resonance imaging (SPRi) and odorant binding proteins (OBPs). OBPs are robust and can reversibly bind VOCs with a micromolar affinity. Herein, three mutant OBPs with tuned binding properties were immobilized on a chip in a microarray format to detect VOCs in liquid. We demonstrated that SPRi was efficient for the analysis of VOCs. The olfactory biosensor exhibited a low limit of dete…

Purification, biophysical characterization and first crystallization trials of the ligand-binding domain of the human T1R3 sweet taste receptor

International audience

Propriétés antigénotoxiques de microconstituants issus de l'ail. Etude in vitro

Ce travail a consisté à évaluer le pouvoir protecteur de composés soufrés de l'ail vis-à-vis de la génotoxicité de différents mutagènes dans un modèle cellulaire humain: les cellules HepG2. La cytotoxicité et la génotoxicité des molécules soufrés ont été mesurées par le test du rouge neutre et le test des comètes. Le sulfure de diallyle (DAS), le disulfure de diallyle (DADS), le thiosulfinate de diallyle (DADSO), la S-allyl cystéine (SAC) et l'allyl mercaptan (AM) ne sont ni cytotoxiques, ni génotoxiques pour les cellules HepG2. Les études d'antigénotoxicité montrent que le co- ou pré-traitement des cellules par les composés soufrés inhibent la génotoxicité de mutagènes directs (peroxyde d'…

Activation of a Sweet Taste Receptor by Oleanane-Type Glycosides from Wisteria sinensis

The phytochemical study of Wisteria sinensis (Sims) DC. (Fabaceae), commonly known as the Chinese Wisteria, led to the isolation of seven oleanane-type glycosides from an aqueous-ethanolic extract of the roots. After successive purifications by various chromatographic methods, like solid/liquid chromatographic methods, vacuum liquid chromatography (VLC), medium pressure liquid chromatography (MPLC), on normal and reverse phase (RP-18 silica gel), and size exclusion chromatography on Sephadex L, their structures were elucidated by an extensive 600 MHz NMR analysis including 1D and 2D NMR experiments as well as ESI-MS. Among the seven isolated saponins, two have never been reported before : 3…

Development of olfactory biosensors for the detection of small molecules by SPRi

National audience

Trace amine associated receptors (TAARs) response to amines are largely affected by sequences variants

The Trace Amine Associated Receptors (TAARs) are a family of chemosensory receptors that recognize volatile amines. These receptors are few in number and highly conserved, compared to regular olfactory receptors. Polymorphisms in the TAAR family can have a drastic impact on our perception of amine compounds. Our study combine numerical simulations with in vitro experiments to reveal the activation mechanisms of the human TAAR5 receptor. The study focused on the hTAAR5-S95P polymorphism, which is found at high frequency in Nordic countries. This mutation affects the perception of trimethylamine (TMA), making individuals less able to perceive the smell of rotten fish caused by this molecule. …

Enzymatic modulation of the bitter taste in Human and Drosophila

Enzymatic modulation of the bitter taste in Human and Drosophila. 4. International Conference on Agricultural and Biological Sciences (ABS 2018)

Decoding sweet taste from chemical structures

International audience

Functional characterization of the ligand binding domain of the cat T1R1 taste receptor

The umami taste receptor is a heterodimeric G-protein coupled receptor (GPCR), composed of two subunits called T1R1 and T1R3. Both subunits are class C GPCRs whose members share a common architecture composed of a large N-terminal domain (NTD) connected to a heptahelical transmembrane domain by a short cysteine-rich domain. Cellular assays combined with molecular docking and site-directed mutagenesis studies have revealed that the NTD of the T1R1 subunit contains the primary binding site for umami stimuli, such as L-glutamate (L-Glu) for humans. Inosine-5’-monophosphate (IMP) binds close to the opening of the NTD, responsible for the characteristic umami synergy between L-Glu and IMP. Funct…

Mechanisms of astringency: Structural alteration of the oral mucosal pellicle by dietary tannins and protective effect of bPRPs

International audience; The interaction of tannins with salivary proteins is involved in astringency. This paper focussed on saliva liningoral mucosae, the mucosal pellicle. Using a cell-based model, the impact of two dietary tannins (EgC and EgCG)on the mucosal pellicle structure and properties was investigated by microscopic techniques. The role of basicProline-Rich-Proteins (bPRPs) in protecting the mucosal pellicle was also evaluated.At low (0.05 mM) tannin concentration, below the sensory detection threshold, the distribution of salivarymucins MUC5B on cells remained unaffected. At 0.5 and 1 mM, MUC5B-tannin aggregates were observed andtheir size increased with tannin concentration and…

Disease sytems chemical biology of flavors

International audience

Garlic and Cancer

Special Issue; International audience; This review summarizes current knowledge on the anticarcinogenic properties of garlic. Collectively epidemiologic studies – mostly casecontrol studies – provide strong evidence that garlic consumption reduces the risk of cancer especially, the risk of gastric and colon cancer. Furthermore many experimental studies demonstrate that organosulfur compounds (OSCs) and garlic extracts can prevent or slow down the carcinogenic process induced by a variety of chemical carcinogens in animals. Garlic and OSCs have been shown to be active during all the stages of carcinogenesis. Several mechanisms have been proposed to explain the cancer-preventive effects of ga…

Triterpenoid saponins from the cultivar “Green Elf” of Pittosporum tenuifolium

Four oleanane-type glycosides were isolated from a horticultural cultivar “Green Elf” of the endemic Pittosporum tenuifolium (Pittosporaceae) from New Zealand: three acylated barringtogenol C glycosides from the leaves, with two previously undescribed 3-O-β-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-β-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, 3-O-β-d-galactopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-β-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C, and the known 3-O-β-d-glucopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-β-d-glucuronopyranosyl-21-O-angeloyl-28-O-acetylbarringtogenol C (Eryngioside L). From the roots, the known 3-O-β-d-glucopyra…

Odorant-binding protein engineering: impact on binding properties

OBP19b is involved in the taste perception of amino acid in Drosophila melanogaster

International audience

Identification of aroma compounds as novel CB1 receptor ligands via in silico approaches

National audience

Optimized vector for functional expression of the human bitter taste receptor TAS2R14 in HEK293 cells

International audience

Development of innovative blends of sweeteners and sweetness enhancers (S&SE) using sweet taste receptor studies

Surface plasmon resonance imaging for sensing volatile organic compounds: Biomimetic olfactory biosensors and optoelectronic nose

National audience; Nowadays, there is a growing demand for the analysis of volatile organic compounds (VOCs) in various domains, including environment, quality control, and medical diagnostics. Traditional analytical methods, though accurate and reliable, require expensive equipment and are often time-consuming and laborious. On the other side, food & fragrance industries employ human sensory panels to evaluate the quality of an odour. However, panellists are expensive to train and employ and they can give biased results. To bridge the gap, we developed different sensor systems inspired by the human nose. Here, a biomimetic olfactory biosensor based on key-and-lock principle was designed us…

Human taste receptors : study of structure-function relationships

Sweet, umami and bitter taste detectors are membrane receptors that belong to the family of G-protein coupled receptors (GPCRs). They are characterized by the existence of a hydrophobic transmembrane domain (TMD) and an activation mechanism that involves a heterotrimeric G protein.Human has 25 bitter taste receptors TAS2R. These receptors belong to class A GPCRs. Their architecture consists of a TMD structured in 7 -helix which form the orthosteric binding site of bitter molecules. The umami taste receptor is a heterodimer composed of the TAS1R1 and TAS1R3 subunits, while the TAS1R2 and TAS1R3 subunits form the sweet taste receptor. Each subunits belongs to the class C GPCRs and shares a c…

Optimization of the production of recombinant brazzein secreted by the yeast pichia pastoris

International audience

Développement d’une méthode d’analyse de la désorption de composés d’arôme par PTR-MS sur un modèle in vitro de muqueuse orale

Développement d’une méthode d’analyse de la désorption de composés d’arôme par PTR-MS sur un modèle in vitro de muqueuse orale. Congrès français de Spectrométrie de Masse et d'Analyse Protéomique (SMAP 2015)

Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine activity

International audience; Introduction: Data from last years suggested that early exposure to endocrine disruptors (EDs) can predispose newborns to endocrine dysfunction of adipocytes, obesity, and associated disorders. The implication of EDs at low doses on adipocyte development has been poorly investigated. For instance, vinclozolin (V) is a dicarboximide fungicide widely used in agriculture since the 90's, alone or in mixture with genistein (G), an isoflavonoid from Leguminosae. This study aims to identify the effect of vinclozolin alone or with genistein, on adipose tissue properties using cell culture.Methods: In steroid-free conditions, 3T3-L1 pre-adipocytes were induced to differentiat…

Perception périphérique des signaux sensoriels. 1- Olfaction

National audience

P259 Identification de nouveaux antagonistes des récepteurs aux endocannabinoïdes à action périphérique susceptibles d’améliorer les paramètres glucido-lipidiques chez la souris obèse

Introduction Le systeme endocannabinoide (SEC) est une cible therapeutique potentielle pour lutter contre l’obesite. Ainsi, le Rimonabant®, un antagoniste des recepteurs aux endocannabinoides 1 (CB1R) diminue la masse corporelle et ameliore les parametres glucido-lipidiques de patients obeses. Neanmoins, ce medicament a ete retire du marche suite a des effets centraux induisant des troubles neuropsychiatriques. L’objectif de cette etude est d’identifier des analogues du Rimonabant® a action peripherique susceptibles d’avoir des effets benefiques sur le metabolisme glucido-lipidique de la souris. Materiels et methodes Des analogues du Rimonabant® ne passant pas la barriere hemato-encephaliqu…

Role of mucosa and mucosal pellicle in aroma persistence

International audience

Odorant binding changes the electrical properties of olfactory receptors at the nanoscale

Olfactory receptors (ORs) comprise the largest multigene family in the vertebrates. They belong to the class A (rhodopsin-like) family of G protein-coupled receptors (GPCRs), which are the most abundant membrane proteins, having widespread, significant roles in signal transduction in cells, and therefore, they are a major pharmacological target. Moreover, ORs displayed high selectivity and sensitivity towards odorant detection, a characteristic that raised the interest for developing biohybrid sensors based on ORs for the detection of volatile compounds. The transduction of odorant binding into cellular signaling by ORs is not well understood and knowing its mechanism would enable developin…

Towards computational biomimetic nose

International audience

Sweet taste receptor-based assay to investigate synergism among sweetener mixtures

The X-ray structure of gurmarin provide new insights into amino acid residues essential for inhibition of the rat sweet taste receptor

International audience; Gurmarin is a polypeptide isolated from the Indian plant Gymnema sylvestre, which specifically suppresses sweet taste in rodents without affecting responses to other basic taste stimuli, such as HCl, NaCl, and quinine. Although the exact mechanism of gurmarin inhibition is not known, it has been shown that gurmarin acts via the T1R2/T1R3 sweet taste receptor. The gurmarin molecule is made of 35 amino-acid residues and three intramolecular disulfide bridges. We report herein the 1.45 Å X-ray structure of gurmarin heterologously produced using the yeast Pichia pastoris. The structure revealed a typical knottin fold, which is compared with previously reported NMR soluti…

Mucin MUC1: a key protein in oral physiology and the molecular mechanisms of sensory perception of astringency