Fig. 7.

Comparison of the structural rearrangement in TM2 and EL1 induced by binding of bulky ligands in β₁AR and β₂AR. (A) Superposition of the cyanopindolol-bound structure (PDB ID 2VT4, cyanopindolol in dark gray, receptor in light gray) and the carvedilol-bound structure (PDB ID 4AMJ, carvedilol in blue, receptor in cyan) of β₁AR shows an outward movement of the extracellular segment of TM2 in the presence of bulky ligand carvedilol, resulting in a 2.3 Å shift of the Cα atom of Gly105 in EL1, and thereby an outward tilting of the extracellular portion of TM2, compared with the cyanopindolol-bound structure. (B) Superposition of the ICI-118551–bound structure (PDB ID 3NY8, ICI-118551 in dark gray, receptor in light gray) and the FAUC50-bound structure (PDB ID 3PDS, FAUC50 in blue, receptor in cyan) of β₂AR shows similar conformations of TM2 and EL1 in the presence of these two ligands. The structures were superimposed by the Cα atoms. ICI-118551, (2S,3S)-1-[(7-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-3-(propan-2-ylamino)butan-2-ol.