The angiotensin II receptors ATIR and AT2R are G protein-coupled receptors(GPCRs) serving as key components of the renin-angiotensin-aldosterone system.ATIR has a central role in the regulation of blood pressure and is a target for anti-hypertensive drugs.While AT2R has a variety of reported effects.To identify the mechanisms that underlie the differences in functional diversity and ligand selectivity between these two receptors,we determined the crystal structures of human ATIR and AT2R bound to their antagonists,respectively,using the recently developed method of serial femtosecond crystallography(SFX) at an X-ray free-electron laser(XFEL).The structures revealed key features of the receptors.Especially,AT2R was captured in an active-like conformation with the helix VIII preventing the recruitment of G proteins or p-arrestins.Structure-activity relationship,docking simulations and mutagenesis studies further revealed the crucial interactions for ligand selectivity.Our results thus provide new insights into the structural basis of the functional diversity of the angiotensin GPCRs,and may guide the design of new selective ligands.