Chemists discover new mode of detection in nose for common class of odours.

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. Firestein et al 2014.

Biologists claim that humans can perceive and distinguish a trillion different odours, but little is known about the underlying chemical processes involved. Researchers from The City College of New York, Duke University and Hebrew University have found an unexpected chemical strategy employed by the mammalian nose to detect chemicals known as aldehydes.

The current study, published in the journal ACS Chemical Biology, found that some of the nose’s many aldehyde receptors don’t detect the aldehyde by its structure and shape directly. Rather, the aldehyde is recognized by its ability to undergo a chemical reaction with water, likely after entering the nose.

Odorant receptors make up a large family of cell membrane proteins that monitor inhaled air on neurons within the nose. Aldehydes, meanwhile, are found in a variety of natural sources like herbs, flowers and fruit. They are typically fresh-smelling chemicals, and synthetic aldehydes are important to the flavour and fragrance industry.

Once exposed to air, aldehydes have a limited lifetime as oxygen slowly converts them into less savoury, even malodorous chemicals.  It’s not surprising then that the nose is adept at detecting aldehydes, and distinguishing them from structurally similar chemical groups.  The team found that for some receptors it’s the aldehyde’s chemical reactivity, not its inherent shape, that tells the nose there are aldehydes in the air.

In the experiments, some of the many odorant receptors that detected the eight-carbon aldehyde octanal recognized the aldehyde portion of the molecule by its ability to morph into a completely different chemical group, known as a gem-diol.  Since this reaction is unique to aldehydes, it serves as a means to discriminate them from similarly shaped chemical groups.

Source:  The City College of New York

 

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.   Firestein et al 2014.
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. Firestein et al 2014.