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PLoS One. 2014 Apr 2;9(4):e93037. doi: 10.1371/journal.pone.0093037. eCollection 2014.

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

Author information

1
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
2
Centre des Sciences du Goût et de l'Alimentation, UMR6265 CNRS, UMR1324 INRA, Bourgogne University, Dijon, France.
3
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
4
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark; INSERM UMR-S973, Molecules Thérapeutiques In Silico, Paris Diderot University, Paris, France.

Abstract

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.

PMID:
24695519
PMCID:
PMC3973694
DOI:
10.1371/journal.pone.0093037
[Indexed for MEDLINE]
Free PMC Article

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