期刊
ACS CHEMICAL BIOLOGY
卷 7, 期 7, 页码 1184-1189出版社
AMER CHEMICAL SOC
DOI: 10.1021/cb300111e
关键词
-
资金
- National Institute on Deafness and Other Communicative Disorders [R01DC010155]
- PSI:Biology GPCR Network [U54 GM094618]
- Boehringer Ingelheim Fonds PhD Fellowship
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 beta(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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据