Domain architecture of six-TM channels. (A) Extracellular view of MlotiK1 structure, a bacterial cyclic nucleotide–regulated potassium channel, representative of the superfamily of six-TM helix cation channels. Subunits are shown in different colors. S1 to S4 compose the S1–S4 domain (structurally equivalent to a voltage sensor domain), and S5 and S6 (a pair from each subunit) form the pore domain. The voltage sensor domains of (B) Kv2.1-chimeric voltage-gated potassium channel and of (C) Kv1.2 voltage-gated potassium channel are shown in more detail. (D) The S1–S4 domain of the MlotiK1 channel. Surface representations correspond to S1, S2, and S3. Helices S4 are shown as a thin helical trace along α-helical segments and as a thick ribbon along 3₁₀ stretches. Conserved positively charged residues, as well as MlotiK1 proline-108, are shown in stick model. The domains are oriented with the extracellular regions at the top of figure and cytoplasmic regions at the bottom. The N termini of S4 are on the extracellular side of the domains.