Figure 3.

The voltage sensors of KCNQ1, hERG, and SCN5A. (A) Structure of the VSD from human KCNQ1 (left) (PDB: 6UZZ) (Sun and Mackinnon, 2020) and hERG (right) (PDB: 5VA2) (Wang and Mackinnon, 2017) in putative activated conformations. Basic residues on S4 (labeled in blue), acidic residues on S2 and S3 (labeled in red), and the phenylalanine residue in the gating charge transfer center (purple) are shown as sticks. The first four basic residues on S4 (R1–R4) in KCNQ1 and the first three (K1–R3) in hERG are located above the charge transfer center. (B) Multiple sequence alignment of VSDs I-IV of SCN5A with the VSDs of human KCNQ1 and hERG. Basic residues in S4 implicated with voltage sensing are colored blue, and acidic or polar residues in S1–S3 suggested to interact with S4 gating charges are colored red. The conserved aromatic residue at the gating charge transfer center in S2 is colored purple. Another tryptophan residue in S3, conserved in the VSDs of Na_V channels and also present in hERG, is colored green.