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

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Karine Marie Laure Audouze, Anne Tromelin, Anne Marie Le Bon, Christine Belloir, Rasmus Koefoed Petersen, Karsten Kristiansen, Søren Brunak, Olivier Taboureau

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.
Original languageEnglish
JournalPloS one
Volume9
Issue number4
Pages (from-to)e93037
Number of pages12
ISSN1932-6203
DOIs
Publication statusPublished - 2014

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