Highlights • Crystal structure of human α2CAR in complex with RS79948 is solved • A specific loosened helix at the top of TM4 in α2CAR is involved in receptor activation • Extracellular regions play a role in determining α2 adrenergic subtype selectivity Summary Adrenergic G-protein-coupled receptors (GPCRs) mediate different cellular signaling pathways in the presence of endogenous catecholamines and play important roles in both physiological and pathological conditions.
