Open AccessElimination of a ligand gating site generates a supersensitive olfactory receptor
Author(s) -
Kanika Sharma,
Gaurav Ahuja,
Ashiq Hussain,
Sabine Balfanz,
Arnd Baumann,
Sigrun Korsching
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep28359
Subject(s) - olfactory receptor , binding site , receptor , ligand (biochemistry) , olfaction , odor , olfactory system , biology , chemistry , biophysics , biochemistry , microbiology and biotechnology , neuroscience
Olfaction poses one of the most complex ligand-receptor matching problems in biology due to the unparalleled multitude of odor molecules facing a large number of cognate olfactory receptors. We have recently deorphanized an olfactory receptor, TAAR13c, as a specific receptor for the death-associated odor cadaverine. Here we have modeled the cadaverine/TAAR13c interaction, exchanged predicted binding residues by site-directed mutagenesis, and measured the activity of the mutant receptors. Unexpectedly we observed a binding site for cadaverine at the external surface of the receptor, in addition to an internal binding site, whose mutation resulted in complete loss of activity. In stark contrast, elimination of the external binding site generated supersensitive receptors. Modeling suggests this site to act as a gate, limiting access of the ligand to the internal binding site and thereby downregulating the affinity of the native receptor. This constitutes a novel mechanism to fine-tune physiological sensitivity to socially relevant odors.