FIGURE 3.

Snapshots from the MD simulations showing interactions in the MHN in the G_q-inactive and G_q-active states. A, schematic representation of the backbone of the AT₁ receptor homology model produced by the I-TASSER server (colored) closely matches the crystal structure of the CXCR4 receptor (gray). of the residues of the MHN are visible as sticks. B and E, in the WT-AT₁ receptor, the side chains of S252^6.47 form an H-bond with the side chain of N294^7.45. The side chains of N111^3.35 and N295^7.46 form an H-bond with D74^2.50. C and F, after the conformational change in the N111G-AT₁ receptor, AngII-N111G-AT₁ receptor, and AngII-WT-AngII receptor; the side chain of S252^6.47 can form H-bonds with backbone amines of Phe²⁹³ and Asn²⁹⁴ or the backbone carbonyl of Ala²⁹¹ (thin line representation) to stabilize the conformational change of TMD7 (red ribbon). The side chain of D74^2.50 can form H-bonds with the side chains of N294^7.45, N295^7.46, and N46^1.50. D and G, in the D74N-AT₁ receptor and AngII-D74N-AT₁ receptor, interactions are as described for B, but additionally include an H-bond between residue D74N^2.50 and N46^1.50 and between N295^7.46 and S115^3.39. Transmembrane domains are shown as colored ribbons (TMD1 = dark blue; TMD2 = light blue; TMD3 = aqua; TMD6 = orange, and TMD7 = red). Side chains are show as sticks. Oxygen atoms are red; nitrogen atoms are blue; hydrogen atoms are white, and carbon atoms are colored according to their TMD. H-bonds predicted by PyMOL are shown as yellow dashed lines.