ArticleProceedings of the National Academy of Sciences of the United States of America2016
Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound α2 homopentamer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed.
- Two Novel Variants in theGenes · 2024Article
- Structure-Based Protein Assembly Simulations Including Various Binding Sites and Conformations.Journal of chemical information and modeling · 2024Article
- Current Progress on Central Cholinergic Receptors as Therapeutic Targets for Alzheimer's Disease.Current Alzheimer research · 2024Review
- A potential cost of evolving epibatidine resistance in poison frogs.BMC biology · 2023Article
- Structural Insights into the Role of β3 nAChR Subunit in the Activation of Nicotinic Receptors.Molecules (Basel, Switzerland) · 2022Article
- Interactions between 2'-fluoro-(carbamoylpyridinyl)deschloroepibatidine analogues and acetylcholine-binding protein inform on potent antagonist activity against nicotinic receptors.Acta crystallographica. Section D, Structural biology · 2022Article
- From Crystal Structures of RgIA4 in Complex withMarine drugs · 2021Article
- Homomeric and Heteromeric α7 Nicotinic Acetylcholine Receptors in Health and Some Central Nervous System Diseases.Membranes · 2021Review
- Personalized Medicine Using Cutting Edge Technologies for Genetic Epilepsies.Current neuropharmacology · 2021Review
- Constructing and Tuning Excitatory Cholinergic Synapses: The Multifaceted Functions of Nicotinic Acetylcholine Receptors inFrontiers in cellular neuroscience · 2021Review
- Functional α6β4 acetylcholine receptor expression enables pharmacological testing of nicotinic agonists with analgesic properties.The Journal of clinical investigation · 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
- Progress in nicotinic receptor structural biology.Neuropharmacology · 2020Review
- Delineating the Site of Interaction of the 5-HTBiophysical journal · 2020Article
- Modulation of theeLife · 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
- Structure-Function of Neuronal Nicotinic Acetylcholine Receptor Inhibitors Derived From Natural Toxins.Frontiers in neuroscience · 2020Review
- Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HTThe Journal of general physiology · 2019Article
- Crystal Structure of the Monomeric Extracellular Domain of α9 Nicotinic Receptor Subunit in Complex With α-Conotoxin RgIA: Molecular Dynamics Insights Into RgIA Binding to α9α10 Nicotinic Receptors.Frontiers in pharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study we report the X-ray crystal structure of the extracellular domain (ECD) of the human neuronal α2 nicotinic acetylcholine receptor (nAChR) subunit in complex with the agonist epibatidine at 3.2 Å. Interestingly, α2 was crystallized as a pentamer, revealing the intersubunit interactions in a wild type neuronal nAChR ECD and the full ligand binding pocket conferred by two adjacent α subunits. The pentameric assembly presents the conserved structural scaffold observed in homologous proteins, as well as distinctive features, providing unique structural information of the binding site between principal and complementary faces. Structure-guided mutagenesis and electrophysiological data confirmed the presence of the α2(+)/α2(-) binding site on the heteromeric low sensitivity α2β2 nAChR and validated the functional importance of specific residues in α2 and β2 nAChR subunits. Given the pathological importance of the α2 nAChR subunit and the high sequence identity with α4 (78%) and other neuronal nAChR subunits, our findings offer valuable information for modeling several nAChRs and ultimately for structure-based design of subtype specific drugs against the nAChR associated diseases.
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.