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...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2018
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| _version_ | 1797058300617949184 |
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| author | Mazzolini, M Arcangeletti, M Marchesi, A Napolitano, L Grosa, D Maity, S Anselmi, C Torre, V |
| author_facet | Mazzolini, M Arcangeletti, M Marchesi, A Napolitano, L Grosa, D Maity, S Anselmi, C Torre, V |
| author_sort | Mazzolini, M |
| collection | OXFORD |
| description | 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 modifcation, 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. |
| first_indexed | 2024-03-06T19:48:31Z |
| format | Journal article |
| id | oxford-uuid:232bc648-defc-4433-a446-3357cc41a805 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:48:31Z |
| publishDate | 2018 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:232bc648-defc-4433-a446-3357cc41a8052022-03-26T11:42:50ZThe gating mechanism in cyclic nucleotide-gated ion channelsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:232bc648-defc-4433-a446-3357cc41a805EnglishSymplectic Elements at OxfordNature Research2018Mazzolini, MArcangeletti, MMarchesi, ANapolitano, LGrosa, DMaity, SAnselmi, CTorre, VCyclic 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 modifcation, 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. |
| spellingShingle | Mazzolini, M Arcangeletti, M Marchesi, A Napolitano, L Grosa, D Maity, S Anselmi, C Torre, V The gating mechanism in cyclic nucleotide-gated ion channels |
| title | The gating mechanism in cyclic nucleotide-gated ion channels |
| title_full | The gating mechanism in cyclic nucleotide-gated ion channels |
| title_fullStr | The gating mechanism in cyclic nucleotide-gated ion channels |
| title_full_unstemmed | The gating mechanism in cyclic nucleotide-gated ion channels |
| title_short | The gating mechanism in cyclic nucleotide-gated ion channels |
| title_sort | gating mechanism in cyclic nucleotide gated ion channels |
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