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Conformational Sensing by a Mammalian Olfactory Receptor
Author(s) -
Liu Min Ting,
Na Mihwa,
Li Yadi,
Biscoe Mark R.,
Ryan Kevin
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001390
Subject(s) - rhodopsin , olfactory receptor , agonist , g protein coupled receptor , octanal , chemistry , olfaction , calcium imaging , stereochemistry , partial agonist , receptor , neuroscience , biophysics , biology , biochemistry , calcium , hexanal , retinal , organic chemistry , chromatography
To identify odors, the mammalian nose deploys hundreds of olfactory receptors (ORs) from the rhodopsin‐like class of the G protein‐coupled receptor superfamily. Odorants having multiple rotatable bonds present a problem for the stereochemical shape‐based matching process assumed to govern the sense of smell through OR–odorant recognition. We conformationally restricted the carbon chain of the odorant octanal to ask whether an OR can respond differently to different odorant conformations. By using calcium imaging to monitor signal transduction in sensory neurons expressing the mouse aldehyde OR, Olfr2, we found that the spatial position of the C7 and C8 carbon atoms of octanal, in relation to its −CHO group, determines whether an aliphatic aldehyde functions as an agonist, partial agonist or antagonist. Our experiments provide evidence that an odorant can manipulate an OR through its intrinsic conformational repertoire, in unexpected analogy to the photon‐controlled aldehyde manipulation observed in rhodopsin.