Figure 3.

Locations of ligand-binding sites in GPCRs of known structure. The structures of a selected set of Class A, B and F receptor-ligand complexes were superimposed and the ligands are shown in surface representation to illustrate the locations of the ligand-binding sites and coloured according to receptor class and subfamily. TM4 from bovine rhodopsin (PDB ID 1HZX) is shown as a reference (left), with the Cα-carbon of the highly conserved W4.50 (Ballesteros-Weinstein numbering) (Ballesteros et al., 1995) displayed as a black sphere. A ‘ruler’ is included (right) for the purpose of ascertaining ligand heights (in Å) as measured from an intracellular boundary point defined by the Cα of Glu150^4.39 along an axis parallel to TM4 from rhodopsin (PDB ID 1HZX). To highlight the unusual location of the small molecule-binding pocket in the CRF₁ receptor, two dashed lines are displayed, indicating the cytoplasmic boundaries of the CRF₁ antagonist and that of doxepin in the H₁ receptor structure. Peptide ligands are marked with an asterisk. This figure was inspired by a recent illustration by Venkatakrishnan et al. (2013).