Figure 8. CLC-2’s gating is illustrated based on our new structural data.

Opening of each protopore requires at least two events – unblock by the N-terminal hairpin (N-ter) and rotation of E_gate away from the permeation pathway. The dashed green arrow represents the Cl⁻ conduction pathway. Hairpin unblock (ball-and-chain gating) is coupled to conformational change of the C-terminal domain (CTD): rotation of the CTD toward the membrane precludes hairpin binding, thus facilitating channel opening. Opening of the channel pore following these two events is depicted for one subunit of the homodimer (filled green arrow).