Molecular interactions at the cytoplasmic end of S2 and S3 are important for efficient gating of KCNQ1. D202/Y171 salt bridge/hydrogen bond with R195 in the closed state (A and B), but not in the open state (C and D). Instead, these residues now interact with R174 in the open state (C and D), an interaction not seen in the closed state (A and B). Key residues in this network of interactions are in space fill. Yellow, D202; green, Y171; magenta, R195; orange, R174. In B and D, the view is looking at the single voltage sensor domain from below.