Porro, Alessandro ; Saponaro, Andrea ; Gasparri, Federica ; Bauer, Daniel ; Gross, Christine ; Pisoni, Matteo ; Abbandonato, Gerardo ; Hamacher, Kay ; Santoro, Bina ; Thiel, Gerhard ; Moroni, Anna (2022)
The HCN domain couples voltage gating and cAMP response in hyperpolarization-activated cyclic nucleotide-gated channels.
In: eLife, 2019, 2019
doi: 10.26083/tuprints-00013344
Article, Secondary publication, Publisher's Version
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| Item Type: | Article |
|---|---|
| Type of entry: | Secondary publication |
| Title: | The HCN domain couples voltage gating and cAMP response in hyperpolarization-activated cyclic nucleotide-gated channels |
| Language: | English |
| Date: | 1 March 2022 |
| Place of Publication: | Darmstadt |
| Year of primary publication: | 2019 |
| Publisher: | eLife Sciences Publications |
| Journal or Publication Title: | eLife |
| Volume of the journal: | 2019 |
| Collation: | 23 Seiten |
| DOI: | 10.26083/tuprints-00013344 |
| Corresponding Links: | |
| Origin: | Secondary publication |
| Abstract: | Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control spontaneous electrical activity in heart and brain. Binding of cAMP to the cyclic nucleotide-binding domain (CNBD) facilitates channel opening by relieving a tonic inhibition exerted by the CNBD. Despite high resolution structures of the HCN1 channel in the cAMP bound and unbound states, the structural mechanism coupling ligand binding to channel gating is unknown. Here we show that the recently identified helical HCN-domain (HCND) mechanically couples the CNBD and channel voltage sensing domain (VSD), possibly acting as a sliding crank that converts the planar rotational movement of the CNBD into a rotational upward displacement of the VSD. This mode of operation and its impact on channel gating are confirmed by computational and experimental data showing that disruption of critical contacts between the three domains affects cAMP- and voltage-dependent gating in three HCN isoforms. |
| Status: | Publisher's Version |
| URN: | urn:nbn:de:tuda-tuprints-133443 |
| Additional Information: | Dataset: https://datadryad.org/stash/dataset/doi:10.5061/dryad.rn85375 |
| Classification DDC: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Divisions: | 10 Department of Biology > Plant Membrane Biophysics |
| Date Deposited: | 01 Mar 2022 08:55 |
| Last Modified: | 19 Sep 2023 18:01 |
| URI: | https://tuprints.ulb.tu-darmstadt.de/id/eprint/13344 |
| PPN: | 505399881 |
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