The gating mechanism in cyclic nucleotide-gated ion channels

• Main Authors: Monica Mazzolini, Manuel Arcangeletti, Arin Marchesi, Luisa M. R. Napolitano, Debora Grosa, Sourav Maity, Claudio Anselmi, Vincent Torre
• Format: Article
• Language: English
• Published: Nature Publishing Group 2018-01-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-017-18499-0

Abstract 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.