Structures and structural models of Ang II type 1 receptor (AT₁R) and ET-1 type A/B receptor (ET_A/BR) complexes. Available structural information for AT₁R and ET_BR relevant for the current study are presented in A–C. (A) Left: the AT₁R in complex with Ang II (PDB ID: 6os0 [40]); right: the active state ET-1/ET_BR structure (orange) complex (PDB ID: 5glh [41]). (B) Homodimer of the active state AT₁R bound with an Ang II analog (PDB ID: 6do1 [42]). (C) AT₂R in complex with Fab and Ang II analog (PDB ID: 5xjm [37]). Receptors are presented as backbone cartoons, for ligands also side-chains are presented as sticks. (D) Complex model of a putative receptor heterodimer with bound agonistic ligands and Fab (surface). This model is based on structural information from A–C, whereby the Fab was oriented by superimposition to AT₁R as observed in (C) for the AT₂R complex. Moreover, an ET_AR homology model together with the AT₁R/Fab complex were superimposed with the AT₁R homodimer as presented in (B). The translucent filled circle highlights putative contact regions between the Fab and both receptors. EL: extracellular loop; H8: helix 8; H1-7: transmembrane helices 1–7; IL: intracellular loop; Nt: N terminus