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The molecular receptive range of an odorant receptor

Abstract

An odor perception is the brain's interpretation of the activation pattern of many peripheral sensory neurons that are differentially sensitive to a wide variety of odors. The sensitivity of these neurons is determined by which of the thousand or so odor receptor proteins they express on their surface. Understanding the odor code thus requires mapping the receptive range of odorant receptors. We have adopted a pharmacological approach that uses a large and diverse pool of odorous compounds to characterize the molecular receptive field of an odor receptor. We found a high specificity for certain molecular features, but high tolerance for others—a strategy that enables the olfactory apparatus to be both highly discriminating, and able to recognize several thousand odorous compounds.

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Figure 1: Strategy used for the selection of potential agonists of OR-I7.
Figure 2: Replacing the aldehyde group reduces activity.
Figure 3: Length of the molecule is important for activity.
Figure 4: Effect of substitution and unsaturation on the activity of C8 aldehydes.
Figure 5: Overlay of the predicted lowest energy conformers of long-chain aldehydes.

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Acknowledgements

We thank T. Loggia and C. Zhang for their assistance with the virus preparation and animal infection, X. Zhang for his help with the Ca2+ imaging experiments, C. Margot and Firminch for chemicals and discussion, B. Schilling and Givaudan-Roure (Vernier, Switzerland) for chemicals, Takasago (Kanagawa, Japan) for neral and geranial, and P. Mombaerts for comments. This work was supported by the Whitehall and McKnight Foundations and the NIDCD.

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Correspondence to Stuart Firestein.

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Araneda, R., Kini, A. & Firestein, S. The molecular receptive range of an odorant receptor. Nat Neurosci 3, 1248–1255 (2000). https://doi.org/10.1038/81774

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