ArticleBiophysical journal2006
cAMP Modulation of the cytoplasmic domain in the HCN2 channel investigated by molecular simulations.
Article in Biophysical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 19 citations in OpenAlex.
- Activation of metabotropic glutamate receptor 1 regulates hippocampal CA1 region excitability in rats with status epilepticus by suppressing the HCN1 channel.Neural regeneration research · 2023Article
- Protein and surface expression of HCN2 and HCN4 subunits in mesocorticolimbic areas after cocaine sensitization.Neurochemistry international · 2019Article
- Bioelectrical control of positional information in development and regeneration: A review of conceptual and computational advances.Progress in biophysics and molecular biology · 2018Review
- Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels.The Journal of biological chemistry · 2015Article
- Cocaine sensitization increases I h current channel subunit 2 (HCN₂) protein expression in structures of the mesocorticolimbic system.Journal of molecular neuroscience : MN · 2013Article
- Energetics of cyclic AMP binding to HCN channel C terminus reveal negative cooperativity.The Journal of biological chemistry · 2012Article
- Regulation of cAMP-dependent protein kinases: the human protein kinase X (PrKX) reveals the role of the catalytic subunit alphaH-alphaI loop.The Journal of biological chemistry · 2010Article
- Gating of HCN channels by cyclic nucleotides: residue contacts that underlie ligand binding, selectivity, and efficacy.Structure (London, England : 1993) · 2007Article
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
The hyperpolarization-activated cyclic nucleotide-modulated (HCN) cation channels are opened by membrane hyperpolarization, while their activation is modulated by the binding of cyclic adenosine monophosphate (cAMP) in the cytoplasm. Here we investigate the molecular basis of cAMP channel modulation by performing molecular dynamics simulations of a segment comprising the C-linker and the cyclic nucleotide binding domain (CNBD) in the presence and absence of cAMP, based on the available crystal structure of HCN2 from mouse. In presence of cAMP, the protein undergoes an oscillation of the quaternary structure on the order of 10 ns, not observed in the apoprotein. In contrast, the absence of ligand causes conformational rearrangements within the CNBDs, driving these domains to a more flexible state, similar to that described in CNBDs of other proteins. This increased flexibility causes a rather disordered movement of the CNBDs, resulting in an inhibitory effect on the channel. We propose that the cAMP-triggered large-scale oscillation plays an important role for the channel's function, being coupled to a motion of the C-linker which, in turn, modulates the gating of the channel.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.