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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Li, Y; Peterlin, Z; Ho, J; Yarnitzky, T; Liu, MT; Fichman, M; Niv, MY; Matsunami, H; Firestein, S; Ryan, K

Published Date

  • November 21, 2014

Published In

Volume / Issue

  • 9 / 11

Start / End Page

  • 2563 - 2571

PubMed ID

  • 25181321

Pubmed Central ID

  • PMC4245160

Electronic International Standard Serial Number (EISSN)

  • 1554-8937

Digital Object Identifier (DOI)

  • 10.1021/cb400290u

Language

  • eng

Conference Location

  • United States