The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding
Issued Date
2022-10
Citation
Shim, Tammy. (2022-10). The Third Extracellular Loop of Mammalian Odorant Receptors Is Involved in Ligand Binding. International Journal of Molecular Sciences, 23(20). doi: 10.3390/ijms232012501
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.
