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The importance of odorant conformation to the binding and activation of a representative olfactory receptor.


ABSTRACT: Olfactory receptors (ORs) form a large family of G protein-coupled receptor proteins (GPCRs) responsible for sensing the ambient chemical environment. The molecular recognition strategies used by ORs to detect and distinguish odorant molecules are unclear. Here, we investigated the variable of odorant carbon chain conformation for an established odorant-OR pair: n-octanal and rat OR-I7. A series of conformationally restricted octanal mimics were tested on live olfactory sensory neurons (OSNs). Our results support a model in which unactivated OR-I7 binds aliphatic aldehydes indiscriminately, and then applies conformational and length filters to distinguish agonists from antagonists. Specific conformers are proposed to activate OR-I7 by steric buttressing of an OR activation pocket. Probing endogenously expressed rat OSNs with octanal and constrained mimics furnished evidence that odorant conformation contributes to an odorant's unique olfactory code signature.

SUBMITTER: Peterlin Z 

PROVIDER: S-EPMC2628580 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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The importance of odorant conformation to the binding and activation of a representative olfactory receptor.

Peterlin Zita Z   Li Yadi Y   Sun Guangxing G   Shah Rohan R   Firestein Stuart S   Ryan Kevin K  

Chemistry & biology 20081201 12


Olfactory receptors (ORs) form a large family of G protein-coupled receptor proteins (GPCRs) responsible for sensing the ambient chemical environment. The molecular recognition strategies used by ORs to detect and distinguish odorant molecules are unclear. Here, we investigated the variable of odorant carbon chain conformation for an established odorant-OR pair: n-octanal and rat OR-I7. A series of conformationally restricted octanal mimics were tested on live olfactory sensory neurons (OSNs). O  ...[more]

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