Figure 1.

An overlay of dark rhodopsin (purple; PDB 1gzm), low pH opsin (green; PDB 3cap), and carazolol-bound β₂AR–T4L (blue; PDB 2rh1) in the vicinity of the ionic lock. In dark rhodopsin, Arg135^3.50 in the conserved D/ERY sequence near the cytoplasmic end of TM3 forms a salt bridge with Glu247^6.30 at the cytoplasmic end of TM6. Arg^3.50 is further stabilized by a salt bridge to the preceding conserved acid at position 3.49 in both rhodopsin and β₂AR. In opsin, Arg135^3.50 interacts with Tyr223^5.58 in TM5, and Glu247^6.30 forms a salt bridge with Lys231^5.66. The homologous ionic lock residues Arg131^3.50 and Glu268^6.30 from the β₂AR are also shown. The amino acids are numbered using the Ballesteros–Weinstein system. Within each helix is a single most conserved residue among the class A GPCRs. This residue is designated x.50, where x is the number of the transmembrane helix. All other residues on that helix are numbered relative to this conserved position.