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The HCN domain couples voltage gating and cAMP response in hyperpolarization-activated cyclic nucleotide-gated channels

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 Science and mathematics > 570 Life sciences, biology
600 Technology, medicine, applied sciences > 610 Medicine and health
Divisions: 10 Department of Biology > Plant Membrane Biophyscis (20.12.23 renamed in Biology of Algae and Protozoa)
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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