PIP ₂ -specific CTD motions of Kir channels. (a) Ribbon and schematic diagrams showing a top-down view of the Kir channel tetramer (PDB accession no. 5KUM). Each subunit is uniquely colored, revealing the ∼80° clockwise rotation of the CTD relative to the TMD of the same subunit. (b) Schematic diagrams of the side view of two opposing (diagonal) subunits; the TMD and CTD from neighboring subunits are in close contact. Gray arrows show the major direction and approximate magnitude of the motion in the absence or presence of PIP₂ and are depicted only on one side of the diagram for clarity. Red vertical double-headed arrows indicate open channel states and K⁺ permeation. (c) Schematic diagrams showing the changes in the dimension of the HBC and G-loop gates by PIP₂ as a result of the motions shown in b. PIP₂ expands the HBC gate while narrowing the G-loop gate as a result of the twisting motions. (d) Schematic diagrams as in b. Gray arrows show the correlated motions of other parts of a tetramer to the widening of the HBC gate between the subunit A and C in the absence (left) or presence of PIP₂ (right). (e) Schematic top-down views of Kir channel tetramers showing the changes in the overall shape of the tetramers as a result of the motions shown in d. The arrows indicate the correlated movements of gates (HBC gate: solid, G-loop gate: dotted) with the expansion of the HBC gate between A and C subunits. In the absence of PIP₂ (left), the expansion leads to narrowing of the other pair. On the other hand, bound PIP₂ leads to positively correlated motions also in the other pair (right).