Identification of odorant-receptor interactions by global mapping of the human odorome

• Published in: PloS one Vol. 9; no. 4; p. e93037
• Main Authors: Audouze, Karine, Tromelin, Anne, Le Bon, Anne Marie, Belloir, Christine, Petersen, Rasmus Koefoed, Kristiansen, Karsten, Brunak, Søren, Taboureau, Olivier
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Analysis; Bibliometrics; Bioinformatics; Biological effects; Biology; Biology and Life Sciences; Cannabinoid CB1 receptors; Chemicals; Chemosensory perception; Chromosome Mapping - methods; Computer and Information Sciences; Food and Nutrition; G proteins; Gene expression; Genetic aspects; Genome, Human - physiology; Humans; Life Sciences; Mammals; Odorant receptors; Odorants; Olfactory receptors; Olfactory system; Pharmacology; Physical Sciences; Physiological aspects; PPAR gamma - genetics; PPAR gamma - metabolism; Proteins; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - metabolism; Receptors; Receptors, Odorant - genetics; Receptors, Odorant - metabolism; Smell; Studies; REPERTOIRE; NETWORK; EPITHELIUM; HUMAN OLFACTORY RECEPTOR; FUNCTIONAL EXPRESSION; DRUG DISCOVERY; CHEMICAL BIOLOGY DATABASE; PPAR-GAMMA; MOLECULAR-BASIS; SMELL
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0093037

The human olfactory system recognizes a broad spectrum of odorants using approximately 400 different olfactory receptors (hORs). Although significant improvements of heterologous expression systems used to study interactions between ORs and odorant molecules have been made, screening the olfactory repertoire of hORs remains a tremendous challenge. We therefore developed a chemical systems level approach based on protein-protein association network to investigate novel hOR-odorant relationships. Using this new approach, we proposed and validated new bioactivities for odorant molecules and OR2W1, OR51E1 and OR5P3. As it remains largely unknown how human perception of odorants influence or prevent diseases, we also developed an odorant-protein matrix to explore global relationships between chemicals, biological targets and disease susceptibilities. We successfully experimentally demonstrated interactions between odorants and the cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor gamma (PPARγ). Overall, these results illustrate the potential of integrative systems chemical biology to explore the impact of odorant molecules on human health, i.e. human odorome.