The gating mechanism in cyclic nucleotide-gated ion channels.

Cyclic nucleotide-gated (CNG) channels mediate transduction in several sensory neurons. These channels use the free energy of CNs' binding to open the pore， a process referred to as gating. CNG channels belong to the superfamily of voltage-gated channels， where the motion of the α-helix S6 controls gating in most of its members. To date， only the open， cGMP-bound， structure of a CNG channel has been determined at atomic resolution， which is inadequate to determine the molecular events underlying gating. By using electrophysiology， site-directed mutagenesis， chemical modification， and Single Molecule Force Spectroscopy， we demonstrate that opening of CNGA1 channels is initiated by the formation of salt bridges between residues in the C-linker and S5 helix. These events trigger conformational changes of the α-helix S5， transmitted to the P-helix and leading to channel opening. Therefore， the superfamily of voltage-gated channels shares a similar molecular architecture but has evolved divergent gating mechanisms.