FIGURE 8.

Superposition of coevolving residues in the ENaC/Degenerin family on cASIC structure. A, highly coevolving residues in the ENaC/Degenerin family computed from Mutual Information Server to Confer Coevolution (MISTIC) (42) superimposed on cASIC crystal structure. A spatially connected allosteric path of coevolving residues lines the thumb, knuckle, and the transmembrane spanning domain TM2. B, zooming in on a specific coevolving interaction between Lys-43 and Asp-454, which may stabilize the transmembrane structure by polar interactions. Charged residues are colored in blue (positive) and red (negative). Cysteines in disulfide bridges are colored in black. Hydrophobic residues are colored in yellow.