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Publication Abstract from PubMed

The alpha2 adrenergic receptors (alpha2ARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. alpha2ARs play important roles in regulating the sympathetic nervous system. Dexmedetomidine is a highly selective alpha2AR agonist used in post-operative patients as an anxiety-reducing, sedative medicine that decreases the requirement for opioids. As is typical for selective alphaAR agonists, dexmedetomidine consists of an imidazole ring and a substituted benzene moiety lacking polar groups, which is in contrast to betaAR-selective agonists, which share an ethanolamine group and an aromatic system with polar, hydrogen-bonding substituents. To better understand the structural basis for the selectivity and efficacy of adrenergic agonists, we determined the structure of the alpha2BAR in complex with dexmedetomidine and Go at a resolution of 2.9 A by single-particle cryo-EM. The structure reveals the mechanism of alpha2AR-selective activation and provides insights into Gi/o coupling specificity.

Activation of the alpha2B adrenoceptor by the sedative sympatholytic dexmedetomidine.,Yuan D, Liu Z, Kaindl J, Maeda S, Zhao J, Sun X, Xu J, Gmeiner P, Wang HW, Kobilka BK Nat Chem Biol. 2020 Mar 9. pii: 10.1038/s41589-020-0492-2. doi:, 10.1038/s41589-020-0492-2. PMID:32152538^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.