A single olfactory receptor specifically binds a set of odorant molecules

Area of Science:

• Olfactory receptor function
• Molecular mechanisms of smell
• Chemosensation

Background:

• The sense of smell relies on olfactory sensory neurons responding to odorants.
• Odorant-receptor interactions are crucial for smell but remain poorly understood.
• Specific structural requirements for odorant activation of olfactory receptors (ORs) are largely unknown.

Purpose of the Study:

• To identify the structural motifs of odorant molecules that activate the mouse olfactory receptor OR912-93.
• To elucidate the recognition mechanism between odorants and OR912-93.

Main Methods:

• Calcium imaging was used to detect odorant responses in cells expressing mouse OR912-93.
• Cells were co-transfected with G(alpha)q and G(alpha)15 proteins to amplify the signaling pathway.
• A library of 70 diverse odorant molecules was screened for activation of OR912-93.

Main Results:

• Ketones with an aliphatic carbon chain length of four or more carbon atoms were identified as activators.
• The carbonyl group's position was critical, with preference for the C2 or C3 position.
• The detection threshold for these specific ketones was as low as 10(-6)-10(-8) M.
• No other tested odorant ligands activated the receptor.

Conclusions:

• Mouse OR912-93 specifically recognizes ketones with particular structural features.
• The human ortholog of OR912-93 is non-functional due to evolutionary mutations, including a stop-mutation.
• This study provides insight into odorant structure-activity relationships for a specific olfactory receptor.