Extended Data Figure 4: Conserved L[M]3.46-I[A]6.37-Y[Y]7.53 microswitch and sodium-binding pocket in AT1R and AT2R.
From: Structural basis for selectivity and diversity in angiotensin II receptors
a, Comparison of the conserved residue triad between the AT1R (green, PDB code 4YAY) and AT2R (cyan) structures shows a rearrangement of interactions consistent with AT2R activation. b, Modelling of the AT2R in a hypothetical inactive state (cyan) based on the AT1R crystal structure template (green) shows that replacement of a large hydrophobic residue in position 6.37, which is conserved in most class A GPCRs, to a rare small Ala2586.37 in AT2R markedly reduces the hydrophobic contact in this region between helices III and VI in the inactive state. c, d, Sodium-binding pocket in AT2R (c) and AT1R (PDB code 4YAY) (d) is shown as a surface with hydrogen bonds between Asn7.46 and Asn3.35 as orange spheres. Putative sodium ion in the AT1R structure (d) is shown as a solid magenta sphere, while the same position in the AT2R structure (c) is marked as a dotted sphere. Potential sodium-coordinating residues are shown as sticks.
