Fig. 1. Comparison of the structures of muscarinic M₁R and angiotensin AT₁R in complex with Gq/11 or biased ligands.

The structure of inactive M₁R (PDB: 5CXV) [89] is superposed with activated M₁R in complex with G11 (panel A, PDB: 6OIJ) [40]. The structure of inactive AT₁R (PDB: 4YAY) [90] is superposed with activated AT₁R in complex with its endogenous ligand angiotensin II (panel B, PDB: 6OS0) [27] and arrestin-biased TRV023 (panel C, PDB: 6OS1) [27]. Shown are side views (left panels), and schematic representation of helices from extracellular (middle panels) and cytoplasmic views (right panel). The positions of helices in the inactive state are shown in light blue, active in red. Inactive receptors are colored purple in left panels. The residues of the active receptors in complex with intracellular partner and balanced or biased agonists are color coded based on the RMSD of α-carbons from the matched residues in the inactive receptor with thresholds of 2.5 Å (cyan), 5 Å (green), 7.5 Å (yellow), 10 Å (orange), and 12.5 Å (red). The direction and extent of displacement of helices are also indicated by arrows. The critical AT₁R residue N111 showing different orientation between structures is indicated by an arrow.