Distinct binding conformations of epinephrine with α- and β-adrenergic receptors.

ABSTRACT: Agonists targeting α₂-adrenergic receptors (ARs) are used to treat diverse conditions, including hypertension, attention-deficit/hyperactivity disorder, pain, panic disorders, opioid and alcohol withdrawal symptoms, and cigarette cravings. These receptors transduce signals through heterotrimeric Gi proteins. Here, we elucidated cryo-EM structures that depict α_2A-AR in complex with Gi proteins, along with the endogenous agonist epinephrine or the synthetic agonist dexmedetomidine. Molecular dynamics simulations and functional studies reinforce the results of the structural revelations. Our investigation revealed that epinephrine exhibits different conformations when engaging with α-ARs and β-ARs. Furthermore, α_2A-AR and β₁-AR (primarily coupled to

SUBMITTER: Lou JS 

PROVIDER: S-EPMC11447022 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature