Fig. 3: Structural features of antagonist-bound and ligand-free (Apo) APJR structures in dimeric forms and the activation hallmarks.

Structural superposition of JN241-APJR with apo-APJR structures, in overall side view (a) and in extracellular view (b). The major conformational change between the two APJR structures is circled in dashed lines. Apo-APJR is colored in yellow. APJR in JN241-APJR complex is colored in light cyan, and JN241 is represented as purple surface. c Overall superposition of the ProtA^AP13 (apelin-13 in yellow) and one protomer from the JN241-bound symmetric APJR dimer structures (JN241 in purple) to show the deeper insertion of apelin-13 compared to JN241 by 5.7 Å. d Overall superposition of the ProtA^AP13 (dark blue) and one protomer from the JN241-bound symmetric APJR dimer structures (light cyan) to highlight the outward movement of TM6 in the apelin-13-bound and Gi-coupled state. e, f Upon activation, the inward movement of TM1, outward movement of TM2 and TM7 at the extracellular side are indicated as arrows. “Y35^1.39-W85^2.50-Y299^7.43” motif is shown with sticks (e). In (f) the outward movement of W261^6.48 exhibits a hallmark of APJR activation.