Aldehyde Recognition and Discrimination by Mammalian Odorant Receptors via Functional Group-Specific Hydration Chemistry

Authors

Yadi Li, CUNY Graduate Center
Zita Peterlin, Department of Biological Sciences, Columbia University, New York, New York 10027, United States
Jianghai Ho, Department of Molecular Genetics and Microbiology, and Neurobiology, Duke University Medical Center, Durham, North Carolina 27710 United States
Tali Yarnitzky, Institute of Biochemistry, Food Science, and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University, Rehovot 76100, Israel
Min Ting Liu, CUNY Graduate Center
Merav Fichman, Institute of Biochemistry, Food Science, and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University, Rehovot 76100, Israel
Masha Y. Niv, Institute of Biochemistry, Food Science, and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University, Rehovot 76100, Israel
Hiroaki Matsunami, Department of Molecular Genetics and Microbiology, and Neurobiology, Duke University Medical Center, Durham, North Carolina 27710 United States
Stuart Firestein, Department of Biological Sciences, Columbia University, New York, New York 10027, United States
Kevin Ryan, CUNY City CollegeFollow

Document Type

Article

Publication Date

September 2015

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.

Comments

This work was originally published in ACS Chemical Biology, available at doi:10.1021/cb400290u.