RGD Reference Report - Agonists for 13 trace amine-associated receptors provide insight into the molecular basis of odor selectivity. - Rat Genome Database

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Agonists for 13 trace amine-associated receptors provide insight into the molecular basis of odor selectivity.

Authors: Ferrero, David M  Wacker, Daniel  Roque, Miguel A  Baldwin, Maude W  Stevens, Raymond C  Liberles, Stephen D 
Citation: Ferrero DM, etal., ACS Chem Biol. 2012 Jul 20;7(7):1184-9. doi: 10.1021/cb300111e. Epub 2012 May 7.
RGD ID: 407430012
Pubmed: PMID:22545963   (View Abstract at PubMed)
PMCID: PMC3401279   (View Article at PubMed Central)
DOI: DOI:10.1021/cb300111e   (Journal Full-text)

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 the 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 β(2) adrenergic receptor structure indicate spatial 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 for studying receptor function, and general insights into the molecular pharmacology of G protein-coupled receptors.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Taar5  (trace amine-associated receptor 5)
Taar7b  (trace amine-associated receptor 7b)
Taar7d  (trace-amine-associated receptor 7d)
Taar7h  (trace amine-associated receptor 7h)
Taar8c  (trace amine-associated receptor 8C)
Taar9  (trace amine-associated receptor 9)


Additional Information