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Updated: Jun 29, 2025
09:53
Real-time In Vitro Monitoring of Odorant Receptor Activation by an Odorant in the Vapor Phase
Published on: April 23, 2019
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Identification of two critical amino acid residues in short-chain aldehyde-responsive odorant receptors
Reina Kanemaki1, Toshiya Hayakawa1, Haruto Kudo1
1Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan.
Journal of Biochemistry
|April 2, 2024
Summary
Specific amino acid changes in olfactory receptors (ORs) significantly improve their function and expression, even without auxiliary proteins. These findings reveal key molecular details for OR functionality and evolution.
Area of Science:
- Molecular Biology
- Neuroscience
- Biochemistry
Background:
- Mammalian olfactory receptors (ORs) are vital for odor detection but often require accessory proteins like Receptor-transporting proteins (RTPs) for functional expression.
- Mouse olfactory receptors Olfr733 and Olfr732 exhibit distinct functional expression despite high sequence homology.
Purpose of the Study:
- To identify specific amino acid residues responsible for the differential functional expression of mouse Olfr733 and Olfr732.
- To elucidate the role of these residues in receptor-ligand interaction, membrane localization, and RTP-independent expression.
Main Methods:
- Site-directed mutagenesis was used to introduce specific amino acid substitutions (G112F and L148P) into Olfr732.
- Functional expression and ligand responsiveness of wild-type and mutant receptors were assessed in heterologous cell systems.
- Analysis of membrane localization and dependence on RTP1S co-expression.
Main Results:
- Mutations G112F and L148P in Olfr732 significantly enhanced RTP-independent expression and ligand responsiveness, mimicking Olfr733.
- Phe112 and Pro148 were identified as critical for aldehyde recognition and enhanced membrane expression, respectively.
- Mouse ORs with Pro at position 4.49 (Pro148) generally show improved membrane expression, particularly with RTP1S.
Conclusions:
- Specific amino acid substitutions, notably Phe112 and Pro148, are key determinants of olfactory receptor functional expression and ligand sensitivity.
- The Pro residue in the fourth transmembrane domain plays a significant role in the structural stability and membrane expression of certain olfactory receptors.
- These findings shed light on the molecular mechanisms underlying OR functionality, evolution, and the development of novel odor detection systems.
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