Aldehyde recognition and discrimination by mammalian odorant receptors via functional group-specific hydration chemistry

Yadi Li, Zita Peterlin, Jianghai Ho, Tali Yarnitzky, Min Ting Liu, Merav Fichman, Masha Y. Niv, Hiroaki Matsunami, Stuart Firestein*, Kevin Ryan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The mammalian odorant receptors (ORs) form a chemical-detecting interface between the atmosphere and the nervous system. This large gene family is composed of hundreds of membrane proteins predicted to form as many unique small molecule binding niches within their G-protein coupled receptor (GPCR) framework, but very little is known about the molecular recognition strategies they use to bind and discriminate between small molecule odorants. Using rationally designed synthetic analogs of a typical aliphatic aldehyde, we report evidence that among the ORs showing specificity for the aldehyde functional group, a significant percentage detect the aldehyde through its ability to react with water to form a 1,1-geminal (gem)-diol. Evidence is presented indicating that the rat OR-I7, an often-studied and modeled OR known to require the aldehyde function of octanal for activation, is likely one of the gem-diol activated receptors. A homology model based on an activated GPCR X-ray structure provides a structural hypothesis for activation of OR-I7 by the gem-diol of octanal. (Figure Presented).

Original languageAmerican English
Pages (from-to)2563-2571
Number of pages9
JournalACS Chemical Biology
Volume9
Issue number11
DOIs
StatePublished - 21 Nov 2014

Bibliographical note

Publisher Copyright:
© 2014 American Chemical Society.

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