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.

The gating mechanism in cyclic nucleotide-gated ion channels / Mazzolini, Monica; Arcangeletti, Manuel; Marchesi, Arin; Napolitano, Luisa Maria Rosaria; Grosa, Debora; Maity, Sourav; Anselmi, Claudio; Torre, Vincent. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 8:1(2018), pp. 1-15. [10.1038/s41598-017-18499-0]

The gating mechanism in cyclic nucleotide-gated ion channels

Mazzolini Monica;Arcangeletti Manuel;Marchesi, Arin;Napolitano, Luisa Maria Rosaria;Grosa, Debora;Maity Sourav;Anselmi, Claudio;Torre Vincent
2018

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.
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www.nature.com/srep/index.html
Mazzolini, Monica; Arcangeletti, Manuel; Marchesi, Arin; Napolitano, Luisa Maria Rosaria; Grosa, Debora; Maity, Sourav; Anselmi, Claudio; Torre, Vincent
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11767/67878
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