Fig. 1.

Inward rectifier K⁺ channels. a Domain architecture of Kir2.1 in the closed (left) and open conformations (right). The C-terminal domain (CTD) is connected to the transmembrane domain (TMD) via a tether helix (light blue). Upon binding of PIP₂ (purple) at the interface between TMD and CTD, the tether helix undergoes a disorder-to-order transition and brings both domains closer together. The G-loop is wedged into the TMD causing the inner helix gate to open. Adapted from ref. ³⁷. b Whole-cell patch clamp electrophysiology of WT Kir2.1 transiently expressed in HEK293FT cells. A representative recording (left) and normalized currents (right) show strong inward rectification ( ± s.e.m., n = 4). c A comparison between KcSA and representative structures of the inward rectifier K⁺ channel family (PDB accession codes are shown in gray) reveals that overall domain architecture is conserved. Channels are shown as blue and accessory protein as green ribbons. Allosteric modulators are indicated with purple circles