Trace amine-associated receptors (TAARs) are vertebrate olfactory receptors. However, ligand recognition properties of TAARs remain poorly understood, as most are ‘orphan receptors’ without known agonists. Here, we identify the first ligands for many rodent TAARs, and classify these receptors into two subfamilies based on phylogeny and binding preference for primary or tertiary amines. Some mouse and rat orthologs have similar response profiles, although independent Taar7 gene expansions led to highly related receptors with altered ligand specificities. Using chimeric TAAR7 receptors, we identified an odor contact site in transmembrane helix III that functions as a selectivity filter. Homology models based on the β2 adrenergic receptor structure indicate close proximity of this site to the ligand. Gain-of-function mutations at this site created olfactory receptors with radically altered odor recognition properties. These studies provide new TAAR ligands, valuable tools to study receptor function, and general insights into the molecular pharmacology of GPCRs.
Single posterior implant-supported restorations significantly increased the percentage (%) of total occlusal pressure in the containing sextant and decreased percentage of total occlusal pressure in the contralateral sextant. When analyzing restorations by exact position, more posterior implant restorations decreased the occlusal pressure applied in anterior dentitions.
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