ArticleProceedings of the National Academy of Sciences of the United States of America2014
Double electron-electron resonance reveals cAMP-induced conformational change in HCN channels.
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 55 papers.
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Who cites it
55 citing papers in PubMed, 92 citations in OpenAlex.
- Advances in EPR Approaches for Studying Structural Properties of Membrane Proteins.Magnetic resonance in chemistry : MRC · 2026Review
- Protein Modeling with DEER Spectroscopy.Annual review of biophysics · 2025Review
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- 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
- A novel approach to modeling side chain ensembles of the bifunctional spin label RX.bioRxiv : the preprint server for biology · 2023Article
- chiLife: An open-source Python package for in silico spin labeling and integrative protein modeling.PLoS computational biology · 2023Article
- Comparative evaluation of spin-label modeling methods for protein structural studies.Biophysical journal · 2022Article
- The structure of the native CNGA1/CNGB1 CNG channel from bovine retinal rods.Nature structural & molecular biology · 2022Article
- The cAMP-signaling cancers: Clinically-divergent disorders with a common central pathway.Frontiers in endocrinology · 2022Review
- Benchmark Test and Guidelines for DEER/PELDOR Experiments on Nitroxide-Labeled Biomolecules.Journal of the American Chemical Society · 2021Article
- Resolving distance variations by single-molecule FRET and EPR spectroscopy using rotamer libraries.Biophysical journal · 2021Article
- Protein functional dynamics from the rigorous global analysis of DEER data: Conditions, components, and conformations.The Journal of general physiology · 2021Article
- Conformational ensemble of a multidomain protein explored by GdBiophysical journal · 2021Article
- Allosteric signaling in C-linker and cyclic nucleotide-binding domain of HCN2 channels.Biophysical journal · 2021Article
- Orientation and dynamics of CuPhysical chemistry chemical physics : PCCP · 2020Article
- Altered conformational sampling along an evolutionary trajectory changes the catalytic activity of an enzyme.Nature communications · 2020Article
- Protein Conformational Dynamics upon Association with the Surfaces of Lipid Membranes and Engineered Nanoparticles: Insights from Electron Paramagnetic Resonance Spectroscopy.Molecules (Basel, Switzerland) · 2020Review
- 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
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Binding of 3',5'-cyclic adenosine monophosphate (cAMP) to hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels regulates their gating. cAMP binds to a conserved intracellular cyclic nucleotide-binding domain (CNBD) in the channel, increasing the rate and extent of activation of the channel and shifting activation to less hyperpolarized voltages. The structural mechanism underlying this regulation, however, is unknown. We used double electron-electron resonance (DEER) spectroscopy to directly map the conformational ensembles of the CNBD in the absence and presence of cAMP. Site-directed, double-cysteine mutants in a soluble CNBD fragment were spin-labeled, and interspin label distance distributions were determined using DEER. We found motions of up to 10 Å induced by the binding of cAMP. In addition, the distributions were narrower in the presence of cAMP. Continuous-wave electron paramagnetic resonance studies revealed changes in mobility associated with cAMP binding, indicating less conformational heterogeneity in the cAMP-bound state. From the measured DEER distributions, we constructed a coarse-grained elastic-network structural model of the cAMP-induced conformational transition. We find that binding of cAMP triggers a reorientation of several helices within the CNBD, including the C-helix closest to the cAMP-binding site. These results provide a basis for understanding how the binding of cAMP is coupled to channel opening in HCN and related channels.
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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.