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The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding.


ABSTRACT: Mammals recognize chemicals in the air via G protein-coupled odorant receptors (ORs). In addition to their orthosteric binding site, other segments of these receptors modulate ligand recognition. Focusing on human hOR1A1, which is considered prototypical of class II ORs, we used a combination of molecular modeling, site-directed mutagenesis, and in vitro functional assays. We showed that the third extracellular loop of ORs (ECL3) contributes to ligand recognition and receptor activation. Indeed, site-directed mutations in ECL3 showed differential effects on the potency and efficacy of both carvones, citronellol, and 2-nonanone.

SUBMITTER: Shim T 

PROVIDER: S-EPMC9604345 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding.

Shim Tammy T   Pacalon Jody J   Kim Won-Cheol WC   Cong Xiaojing X   Topin Jérémie J   Golebiowski Jérôme J   Moon Cheil C  

International journal of molecular sciences 20221018 20


Mammals recognize chemicals in the air via G protein-coupled odorant receptors (ORs). In addition to their orthosteric binding site, other segments of these receptors modulate ligand recognition. Focusing on human hOR1A1, which is considered prototypical of class II ORs, we used a combination of molecular modeling, site-directed mutagenesis, and in vitro functional assays. We showed that the third extracellular loop of ORs (ECL3) contributes to ligand recognition and receptor activation. Indeed,  ...[more]

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