ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 80 citations in OpenAlex.
- Lipid bilayers determine allostery but not intrinsic affinity of cAMP to pacemaker channels.Nature communications · 2026Article
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- Extracellular salt bridge networks around S4 implicated in HCN channel gating and heart disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Exploring characteristic features for effective HCN1 channel inhibition using integrated analytical approaches: 3D QSAR, molecular docking, homology modelling, ADME and molecular dynamics.European biophysics journal : EBJ · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Role of HCN channels in the functions of basal ganglia and Parkinson's disease.Cellular and molecular life sciences : CMLS · 2024Review
- A high affinity switch for cAMP in the HCN pacemaker channels.Nature communications · 2024Article
- Conformational trajectory of allosteric gating of the human cone photoreceptor cyclic nucleotide-gated channel.Nature communications · 2023Article
- Discovery of a small-molecule inhibitor of the TRIP8b-HCN interaction with efficacy in neurons.The Journal of biological chemistry · 2022Article
- Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- Validation of the binding stoichiometry between HCN channels and their neuronal regulator TRIP8b by single molecule measurements.Frontiers in physiology · 2022Article
- Hippocampal cAMP regulates HCN channel function on two time scales with differential effects on animal behavior.Science translational medicine · 2021Article
- IProgress in biophysics and molecular biology · 2021Review
- Gating movements and ion permeation in HCN4 pacemaker channels.Molecular cell · 2021Article
- Understanding Docking Complexes of Macromolecules Using HADDOCK: The Synergy between Experimental Data and Computations.Bio-protocol · 2020Article
- Rational design of a mutation to investigate the role of the brain protein TRIP8b in limiting the cAMP response of HCN channels in neurons.The Journal of general physiology · 2020Article
- Alterations in SUMOylation of the hyperpolarization-activated cyclic nucleotide-gated ion channel 2 during persistent inflammation.European journal of pain (London, England) · 2020Article
- Article
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
cAMP signaling in the brain mediates several higher order neural processes. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels directly bind cAMP through their cytoplasmic cyclic nucleotide binding domain (CNBD), thus playing a unique role in brain function. Neuronal HCN channels are also regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit that antagonizes the effects of cAMP by interacting with the channel CNBD. To unravel the molecular mechanisms underlying the dual regulation of HCN channel activity by cAMP/TRIP8b, we determined the NMR solution structure of the HCN2 channel CNBD in the cAMP-free form and mapped on it the TRIP8b interaction site. We reconstruct here the full conformational changes induced by cAMP binding to the HCN channel CNBD. Our results show that TRIP8b does not compete with cAMP for the same binding region; rather, it exerts its inhibitory action through an allosteric mechanism, preventing the cAMP-induced conformational changes in the HCN channel CNBD.
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Registered trials
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.