Fig. 1. Cryo-EM structures of the _dimAPJR^AP13-Gi and _monAPJR^AP13-Gi complexes and comparisons with _dimAPJR^ELA-Gi complex.

a A model demonstrating the potential pharmacological effects induced by two endogenous peptide ligands on APJR. Created in BioRender. Yue, Y. (2025) https://BioRender.com/p30r650. b Cryo-EM maps and structure models of _dimAPJR^AP13-Gi complex and _monAPJR^AP13-Gi complex. Protomer primarily coupled with Gi is termed ProtA and non-coupled is termed ProtB. Apelin-13, yellow; ProtA^AP13, blue; ProtB^AP13, pink; _monAPJR^AP13, green. Gα_i, Gβ and Gγ are in light cyan, light green and light blue, respectively. The ICL1 and ICL2 regions were disordered, and in ProtB, only the main chain was modeled due to insufficient side-chain density. Structural comparison between _dimAPJR^AP13-Gi and _dimAPJR^ELA-Gi (PDB ID: 7W0N) in overall side view (c), intracellular view (d), and extracellular view (e), respectively.