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 Î±-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 Î±-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.
|Titolo:||The gating mechanism in cyclic nucleotide-gated ion channels|
|Autori:||Mazzolini, Monica; Arcangeletti, Manuel; Marchesi, Arin; Napolitano Luisa, M. R.; Grosa, Debora; Maity, Sourav; Anselmi, Claudio; Torre, Vincent|
|Data di pubblicazione:||2018|
|Numero di Articolo:||45|
|Digital Object Identifier (DOI):||10.1038/s41598-017-18499-0|
|Appare nelle tipologie:||1.1 Journal article|