Structural insights into ligand recognition, activation, and signaling of the α_2A adrenergic receptor.

ABSTRACT: The α_2A adrenergic receptor (α_2AAR) is a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor that mediates important physiological functions in response to the endogenous neurotransmitters norepinephrine and epinephrine, as well as numerous chemically distinct drugs. However, the molecular mechanisms of drug actions remain poorly understood. Here, we report the cryo-electron microscopy structures of the human α_2AAR-GoA complex bound to norepinephrine and three imidazoline derivatives (brimonidine, dexmedetomidine, and oxymetazoline). Together with mutagenesis and functional data, these structures provide important insights into the molecular basis of ligand recognition, activation, and signaling at the α_2AAR. Further st

SUBMITTER: Xu J 

PROVIDER: S-EPMC8896805 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature