Conformational Sensing by a Mammalian Olfactory Receptor

Abstract

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jul 21, 2020
Source ID
10.1002/chem.202001390

Entities

People

  • Kevin Ryan
  • Mark R. Biscoe
  • Mihwa Na
  • Min Ting Liu
  • Yadi Li

Organizations

  • Army Research Office
  • CUNY Graduate School and University Center
  • City College of New York
  • City University of New York
  • National Institute of General Medical Sciences
  • National Institute on Minority Health and Health Disparities
  • United States Army Research Laboratory

Tags

Fields of Study

  • Biology

Readers

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  • Organic Chemistry
  • Vision Science/Vision Psychology/Cognitive Neuroscience.