Functional and structural characterization of interactions between opposite subunits in HCN pacemaker channels

Simple item page
dc.contributor.authorKondapuram, Mahesh
dc.contributor.authorFrieg, Benedikt
dc.contributor.authorYĆ¼ksel, Sezin
dc.contributor.authorSchwabe, Tina
dc.contributor.authorSattler, Christian
dc.contributor.authorLelle, Marco
dc.contributor.authorSchweinitz, Andrea
dc.contributor.authorSchmauder, Ralf
dc.contributor.authorBenndorf, Klaus
dc.contributor.authorGohlke, Holger
dc.contributor.authorKusch, Jana
dc.date.accessioned2021-08-05T19:55:28Z
dc.date.available2021-08-05T19:55:28Z
dc.date.issued2021-08-05
dc.description.abstractHyperpolarization-activated and cyclic nucleotide (HCN) modulated channels are tetrameric cation channels. In each of the four subunits, the intracellular cyclic nucleotide-binding domain (CNBD) is coupled to the transmembrane domain via a helical structure, the C-linker. High-resolution channel structures suggest that the C-linker enables functionally relevant interactions with the opposite subunit, which might be critical for coupling the conformational changes in the CNBD to the channel pore. We combined mutagenesis, patch-clamp technique, confocal patch-clamp fluorometry, and molecular dynamics simulations to show that residue K464 of the C-linker is essential for stabilizing the closed state of the mHCN2 channel by forming interactions with the opposite subunit. MD simulations revealed that both cAMP and K464E induce a rotation of the intracellular domain relative to the channel pore, weakening the autoinhibitory effect of the unoccupied CL-CNBD region. The adopted poses are in excellent agreement with structural results.en
dc.identifier.urihttps://researchdata.hhu.de/handle/entry/98
dc.identifier.urihttp://dx.doi.org/10.25838/d5p-27
dc.language.isoenen
dc.publisherN/Aen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectHCN channelen
dc.subjectmolecular dynamics simulationsen
dc.subjectsubunit interactionen
dc.subjectpatch-clamp techniqueen
dc.subjectconfocal patch-clamp fluorometryen
dc.titleFunctional and structural characterization of interactions between opposite subunits in HCN pacemaker channelsen
dc.typeDataseten

Files

Original bundle
Now showing 1 - 3 of 3
No Thumbnail Available
Name:
DATA_SOURCE_MDsimulation_Modelling.xlsx
Size:
34.15 KB
Format:
Microsoft Excel XML
Description:
MD simulations data
Download
No Thumbnail Available
Name:
Data Source Electrophysiology.xlsx
Size:
35.21 KB
Format:
Microsoft Excel XML
Description:
Electrophysiological data
Download
No Thumbnail Available
Name:
Data Source Patch-Clamp-Fluorometry.xlsx
Size:
9.29 KB
Format:
Microsoft Excel XML
Description:
Fluorescence data
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
3.32 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Computational Pharmaceutical Chemistry and Molecular Informatics Group