ArticleProceedings of the National Academy of Sciences of the United States of America2008
Spontaneous conformational change and toxin binding in alpha7 acetylcholine receptor: insight into channel activation and inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed.
- Modern venomics-Current insights, novel methods, and future perspectives in biological and applied animal venom research.GigaScience · 2022Article
- Native or Non-Native Protein-Protein Docking Models? Molecular Dynamics to the Rescue.Journal of chemical theory and computation · 2021Article
- Spatial Structure and Activity of Synthetic Fragments of Lynx1 and of Nicotinic Receptor Loop C Models.Biomolecules · 2020Article
- A Computational Analysis of the Factors Governing the Dynamics of α7 nAChR and Its Homologs.Biophysical journal · 2020Article
- Nicotinic receptor pharmacology in silico: Insights and challenges.Neuropharmacology · 2020Review
- Interactions of the α3β2 Nicotinic Acetylcholine Receptor Interfaces with α-Conotoxin LsIA and its Carboxylated C-terminus Analogue: Molecular Dynamics Simulations.Marine drugs · 2020Article
- In Silico Modeling of the α7 Nicotinic Acetylcholine Receptor: New Pharmacological Challenges Associated with Multiple Modes of Signaling.Mini reviews in medicinal chemistry · 2020Review
- Effects of C-Terminal Carboxylation on α-Conotoxin LsIA Interactions with Human α7 Nicotinic Acetylcholine Receptor: Molecular Simulation Studies.Marine drugs · 2019Article
- Ketamine Inhibition of the Pentameric Ligand-Gated Ion Channel GLIC.Biophysical journal · 2017Article
- Gating Motions and Stationary Gating Properties of Ionotropic Glutamate Receptors: Computation Meets Electrophysiology.Accounts of chemical research · 2017Review
- Article
- Conformational changes in acetylcholine binding protein investigated by temperature accelerated molecular dynamics.PloS one · 2014Article
- A gating mechanism of pentameric ligand-gated ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2013Review
- An NMDA receptor gating mechanism developed from MD simulations reveals molecular details underlying subunit-specific contributions.Biophysical journal · 2013Article
- Asymmetric ligand binding facilitates conformational transitions in pentameric ligand-gated ion channels.Journal of the American Chemical Society · 2013Article
- GABA binding to an insect GABA receptor: a molecular dynamics and mutagenesis study.Biophysical journal · 2012Article
- Size matters in activation/inhibition of ligand-gated ion channels.Trends in pharmacological sciences · 2012Review
- Gating mechanism of a P2X4 receptor developed from normal mode analysis and molecular dynamics simulations.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Atomistic mechanism for the activation and desensitization of an AMPA-subtype glutamate receptor.Nature communications · 2011Article
- Assessing protein loop flexibility by hierarchical Monte Carlo sampling.Journal of chemical theory and computation · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Nicotinic AChRs (nAChRs) represent a paradigm for ligand-gated ion channels. Despite intensive studies over many years, our understanding of the mechanisms of activation and inhibition for nAChRs is still incomplete. Here, we present molecular dynamics (MD) simulations of the alpha7 nAChR ligand-binding domain, both in apo form and in alpha-Cobratoxin-bound form, starting from the respective homology models built on crystal structures of the acetylcholine-binding protein. The toxin-bound form was relatively stable, and its structure was validated by calculating mutational effects on the toxin-binding affinity. However, in the apo form, one subunit spontaneously moved away from the conformation of the other four subunits. This motion resembles what has been proposed for leading to channel opening. At the top, the C loop and the adjacent beta7-beta8 loop swing downward and inward, whereas at the bottom, the F loop and the C terminus of beta10 swing in the opposite direction. These swings appear to tilt the whole subunit clockwise. The resulting changes in solvent accessibility show strong correlation with experimental results by the substituted cysteine accessibility method upon addition of acetylcholine. Our MD simulation results suggest a mechanistic model in which the apo form, although predominantly sampling the "closed" state, can make excursions into the "open" state. The open state has high affinity for agonists, leading to channel activation, whereas the closed state upon distortion has high affinity for antagonists, leading to inhibition.
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.