Figure 7.

Allosteric interface extended by water-mediated interactions. (A) Betweenness centralities calculated with $\left(C_B^w\right)$ and without $\left(C_B^o\right)$ water-mediated interaction for each receptor state. Water-free contact between two residues is defined if any heavy atom in one residue is within 4 Å from other residue; water-mediated contact between two residues is defined if a water oxygen is shared by two residues within 3.5 Å. (B) $\Delta C_B$ (≡ $C_B^w$ − $C_B^o$ ) for each state. Large values of $\Delta C_B$ are identified around the TM7 helix in the agonist-bound active state (red arrow). (C) Regions with $C_B^w$ > 0.07 (corresponding to the top 10% of $C_B$ values, blue mesh, and blue arrows in (A)) and $\Delta C_B$ > 0.03 (magenta surface in (C) and a magenta arrow in (B)) are demarcated on the structure of the active state. The microswitch residues are depicted as spheres. To see this figure in color, go online.