TY  - JOUR
AU  - Sharma, Kanika
AU  - Ahuja, Gaurav
AU  - Hussain, Ashiq
AU  - Balfanz, Sabine
AU  - Baumann, A.
AU  - Korsching, Sigrun I.
TI  - Elimination of a ligand gating site generates a supersensitive olfactory receptor
JO  - Scientific reports
VL  - 6
SN  - 2045-2322
CY  - London
PB  - Nature Publishing Group
M1  - FZJ-2016-03498
SP  - 28359 
PY  - 2016
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000378197600001
C6  - pmid:27323929
DO  - DOI:10.1038/srep28359
UR  - https://juser.fz-juelich.de/record/810932
ER  -