Schematic of the hERG3 channel subunit.
Left side, hERG, which is part of the EAG family of ion channels, has four subunits, each shown as a quadrant, that assemble to form a tetrameric structure as shown in the circular schematic on the left. Right side, each subunit contains a transmembrane region, as well as cytoplasmic N- and C-terminal regions. The transmembrane region contains voltage sensor (helices S1–S4, dark gray) and pore-forming (helices S5 and S6, magenta) domains inside the membrane bilayer. The C-terminal cytoplasmic region contains a cyclic nucleotide-binding homology domain (CNBHD, red), which is connected to the transmembrane region via a structured domain usually referred to as the C-linker. The N-terminal cytoplasmic region (∼400 residues) contains a region that is known as the eag domain (residues 1–135), which itself comprises a Cap domain (residues 1–26, light blue) and a PAS domain (residues 27–135, purple). This eag domain fragment (residues 1–135) has been expressed in this work and is referred to as hERG3-eag in this paper.