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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Mapping / methods*
  • Genome, Human / physiology*
  • Humans
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptors, Odorant / genetics*
  • Receptors, Odorant / metabolism

Substances

  • PPAR gamma
  • Receptor, Cannabinoid, CB1
  • Receptors, Odorant

Grant support

The work was supported by the GENDINOB project granted by the Danish Council for Strategic Research and the Innovative Medicines Initiative Joint Undertaking (IMI-JU) for the eTOX project (115002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.