ArticleeLife2016
Structure and dynamics underlying elementary ligand binding events in human pacemaking channels.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed.
- Single-molecule nanophotonic resolution of binding dynamics from apo to fully liganded for a cyclic nucleotide-gated ion channel in cell-derived vesicles.bioRxiv : the preprint server for biology · 2026Article
- Lipid bilayers determine allostery but not intrinsic affinity of cAMP to pacemaker channels.Nature communications · 2026Article
- Ligand Binding Dynamics of Ion Channels and GPCRs Using Single-Molecule Fluorescence.Annual review of biophysics · 2026Review
- Membrane-forming phospholipids allosterically modulate native-state prolyl isomerization in a CNG channel.Protein science : a publication of the Protein Society · 2025Article
- 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
- Article
- Ligand-Coupled Conformational Changes in a Cyclic Nucleotide-Gated Ion Channel Revealed by Time-Resolved Transition Metal Ion FRET.bioRxiv : the preprint server for biology · 2024Article
- Bioelectricity and molecular signaling.Biophysical journal · 2024Article
- Anisotropic Network Analysis of Open/Closed HCN4 Channel Advocates Asymmetric Subunit Cooperativity in cAMP Modulation of Gating.Journal of chemical information and modeling · 2024Article
- A Sequential Binding Mechanism for 5' Splice Site Recognition and Modulation for the Human U1 snRNP.bioRxiv : the preprint server for biology · 2024Article
- cAMP binding to closed pacemaker ion channels is cooperative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Strategies for Overcoming the Single-Molecule Concentration Barrier.ACS measurement science au · 2023Review
- Fisetin decreases the duration of ictal-like discharges in mouse hippocampal slices.Journal of biological physics · 2022Article
- Enlightening activation gating in P2X receptors.Purinergic signalling · 2022Review
- Gold Ion Beam Milled Gold Zero-Mode Waveguides.Nanomaterials (Basel, Switzerland) · 2022Article
- Electrochemical Zero-Mode Waveguide Potential-Dependent Fluorescence of Glutathione Reductase at Single-Molecule Occupancy.Analytical chemistry · 2022Article
- Zero-mode waveguides and nanopore-based sequencing technologies accelerate single-molecule studies.Biophysics and physicobiology · 2022Article
- Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel.Nature communications · 2021Article
- Unsupervised selection of optimal single-molecule time series idealization criterion.Biophysical journal · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Although molecular recognition is crucial for cellular signaling, mechanistic studies have relied primarily on ensemble measures that average over and thereby obscure underlying steps. Single-molecule observations that resolve these steps are lacking due to diffraction-limited resolution of single fluorophores at relevant concentrations. Here, we combined zero-mode waveguides with fluorescence resonance energy transfer (FRET) to directly observe binding at individual cyclic nucleotide-binding domains (CNBDs) from human pacemaker ion channels critical for heart and brain function. Our observations resolve the dynamics of multiple distinct steps underlying cyclic nucleotide regulation: a slow initial binding step that must select a 'receptive' conformation followed by a ligand-induced isomerization of the CNBD. X-ray structure of the apo CNBD and atomistic simulations reveal that the isomerization involves both local and global transitions. Our approach reveals fundamental mechanisms underpinning ligand regulation of pacemaker channels, and is generally applicable to weak-binding interactions governing a broad spectrum of signaling processes.
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.