Sharma, Kanika, Ahuja, Gaurav ORCID: 0000-0002-2837-9361, Hussain, Ashiq, Balfanz, Sabine ORCID: 0000-0002-7082-3999, Baumann, Arnd ORCID: 0000-0001-9456-7275 and Korsching, Sigrun I. (2016). Elimination of a ligand gating site generates a supersensitive olfactory receptor. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sharma, KanikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahuja, GauravUNSPECIFIEDorcid.org/0000-0002-2837-9361UNSPECIFIED
Hussain, AshiqUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balfanz, SabineUNSPECIFIEDorcid.org/0000-0002-7082-3999UNSPECIFIED
Baumann, ArndUNSPECIFIEDorcid.org/0000-0001-9456-7275UNSPECIFIED
Korsching, Sigrun I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-272077
DOI: 10.1038/srep28359
Journal or Publication Title: Sci Rep
Volume: 6
Date: 2016
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROTEIN-COUPLED RECEPTOR; MOUSE ODORANT RECEPTOR; FUNCTIONAL-CHARACTERIZATION; CONFORMATIONAL DYNAMICS; CRYSTAL-STRUCTURE; BINDING-SITE; IDENTIFICATION; RHODOPSIN; HONEYBEE; ACCURACYMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27207

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