Elimination of a ligand gating site generates a supersensitive olfactory receptor

Kanika Sharma1, Gaurav Ahuja1, Ashiq Hussain1

  • 1Institute of Genetics, Biocenter, University at Cologne, Zülpicherstrasse 47a, 50674 Cologne, Germany.

Scientific Reports
|June 22, 2016
PubMed

Insights

Researchers discovered a novel dual binding site mechanism in the olfactory receptor TAAR13c for the odor cadaverine. An external site acts as a gate, regulating sensitivity to socially relevant odors.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Sensory Biology

Background:

  • Olfaction involves complex ligand-receptor interactions with numerous odorants and receptors.
  • The olfactory receptor TAAR13c was recently identified as a specific receptor for cadaverine, a death-associated odor.

Purpose of the Study:

  • To model the interaction between cadaverine and TAAR13c.
  • To investigate the functional role of identified binding sites through mutagenesis.
  • To elucidate the mechanism of odorant sensitivity regulation in olfaction.

Main Methods:

  • Computational modeling of ligand-receptor interactions.
  • Site-directed mutagenesis of TAAR13c.
  • Functional assays to measure receptor activity.

Main Results:

  • A dual binding site for cadaverine was identified: one internal and one external.
  • Mutation of the internal site abolished receptor activity.
  • Elimination of the external binding site led to supersensitive receptors.

Conclusions:

  • The external binding site acts as a regulatory gate, controlling ligand access to the internal site.
  • This novel mechanism fine-tunes receptor affinity and physiological sensitivity to odors.
  • Findings provide new insights into the regulation of olfactory perception for socially relevant cues.

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