ECL1 sequence alignment and homology model. (A) Sequence alignment of ECL1 in CFTR proteins from nine species. Charged residues are indicated in red. Asterisks indicate residues conserved in multiple species. D110, E116, and R117 are disease-related and conserved residues labeled with arrows. (B) Top view of the homology model of CFTR (McCarty laboratory model; Rahman et al., 2013) with charged acidic (green) and basic (red) amino acids shown as spheres; model prepared with PyMOL. (left) Closed state (equivalent to the state where the NBDs are fully dedimerized). (right) Open state. TM1-6 is indicated in brown shades, and TM7-12 is indicated in blue shades.