ArticleStructure (London, England : 1993)2007
Gating of HCN channels by cyclic nucleotides: residue contacts that underlie ligand binding, selectivity, and efficacy.
Article in Structure (London, England : 1993), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 105 citations in OpenAlex.
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- An inter-subunit path is required for entropically-driven and negatively cooperative binding of cyclic nucleotides in the HCN2 channel.Communications biology · 2026Article
- Combination of Autodisplay and Dynamic Pharmacophore Modeling Reveals New Insights into Cyclic Nucleotide Binding in Hyperpolarization-Activated and Cyclic Nucleotide-Gated Ion Channel 4 (HCN4).ACS pharmacology & translational science · 2024Article
- A high affinity switch for cAMP in the HCN pacemaker channels.Nature communications · 2024Article
- Biology, Pathobiology and Gene Therapy of CNG Channel-Related Retinopathies.Biomedicines · 2023Review
- Altered cyclic nucleotide binding and pore opening in a diseased human HCN4 channel.Biophysical journal · 2022Article
- Uncoupling of Voltage- and Ligand-Induced Activation in HCN2 Channels by Glycine Inserts.Frontiers in physiology · 2022Article
- Optogenetic modulation of real-time nanoscale dynamics of HCN channels using photoactivated adenylyl cyclases.RSC chemical biology · 2021Article
- Allosteric signaling in C-linker and cyclic nucleotide-binding domain of HCN2 channels.Biophysical journal · 2021Article
- 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
- Article
- Binding and structural asymmetry governs ligand sensitivity in a cyclic nucleotide-gated ion channel.The Journal of general physiology · 2019Article
- Hydrophobic alkyl chains substituted to the 8-position of cyclic nucleotides enhance activation of CNG and HCN channels by an intricate enthalpy - entropy compensation.Scientific reports · 2018Article
- All four subunits of HCN2 channels contribute to the activation gating in an additive but intricate manner.The Journal of general physiology · 2018Article
- Article
- Article
- Ligand binding and activation properties of the purified bacterial cyclic nucleotide-gated channel SthK.The Journal of general physiology · 2018Article
- Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy.International journal of molecular sciences · 2018Review
- Structural insights into the mechanisms of CNBD channel function.The Journal of general physiology · 2018Review
- Free energy landscape remodeling of the cardiac pacemaker channel explains the molecular basis of familial sinus bradycardia.The Journal of biological chemistry · 2017Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cyclic nucleotides (cNMPs) regulate the activity of various proteins by interacting with a conserved cyclic nucleotide-binding domain (CNBD). Although X-ray crystallographic studies have revealed the structures of several CNBDs, the residues responsible for generating the high efficacy with which ligand binding leads to protein activation remain unknown. Here, we combine molecular dynamics simulations with mutagenesis to identify ligand contacts important for the regulation of the hyperpolarization-activated HCN2 channel by cNMPs. Surprisingly, out of 7 residues that make strong contacts with ligand, only R632 in the C helix of the CNBD is essential for high ligand efficacy, due to its selective stabilization of cNMP binding to the open state of the channel. Principal component analysis suggests that a local movement of the C helix upon ligand binding propagates through the CNBD of one subunit to the C linker of a neighboring subunit to apply force to the gate of the channel.
Indexed as
Identifiers
What OpenQuestion holds
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.