ArticleProceedings of the National Academy of Sciences of the United States of America2015
Molecular blueprint of allosteric binding sites in a homologue of the agonist-binding domain of the α7 nicotinic acetylcholine receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 115 citations in OpenAlex.
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- Chimeric Approach to Identify Molecular Determinants of Nicotinic Acetylcholine Receptors.International journal of molecular sciences · 2026Review
- Long COVID - a critical disruption of cholinergic neurotransmission?Bioelectronic medicine · 2025Review
- Generation of nanobodies acting as silent and positive allosteric modulators of the α7 nicotinic acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2023Article
- Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?Bioelectronic medicine · 2023Article
- Unravelling the allosteric binding mode of αD-VxXXB at nicotinic acetylcholine receptors.Frontiers in pharmacology · 2023Article
- Pharmacophore Mapping Combined with dbCICA Reveal New Structural Features for the Development of Novel Ligands Targeting α4β2 and α7 Nicotinic Acetylcholine Receptors.Molecules (Basel, Switzerland) · 2022Article
- A Functional Interaction Between Y674-R685 Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor.Molecular neurobiology · 2022Article
- Stable desensitization of αEuropean journal of pharmacology · 2021Article
- The Allosteric Activation of α7 nAChR by α-Conotoxin MrIC Is Modified by Mutations at the Vestibular Site.Toxins · 2021Article
- Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor.RSC advances · 2021Article
- Beyond Alkaloids: Novel Bioactive Natural Products FromFrontiers in pharmacology · 2021Review
- 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
- Differing Activity Profiles of the Stereoisomers of 2,3,5,6TMP-TQS, a Putative Silent Allosteric Modulator ofMolecular pharmacology · 2020Article
- Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors.International journal of molecular sciences · 2020Article
- Tetrapeptide Ac-HAEE-NHInternational journal of molecular sciences · 2020Article
- Article
- Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.Neuropharmacology · 2020Review
- Modulation of theeLife · 2020Article
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Authors and funding
12 authors at 6 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The α7 nicotinic acetylcholine receptor (nAChR) belongs to the family of pentameric ligand-gated ion channels and is involved in fast synaptic signaling. In this study, we take advantage of a recently identified chimera of the extracellular domain of the native α7 nicotinic acetylcholine receptor and acetylcholine binding protein, termed α7-AChBP. This chimeric receptor was used to conduct an innovative fragment-library screening in combination with X-ray crystallography to identify allosteric binding sites. One allosteric site is surface-exposed and is located near the N-terminal α-helix of the extracellular domain. Ligand binding at this site causes a conformational change of the α-helix as the fragment wedges between the α-helix and a loop homologous to the main immunogenic region of the muscle α1 subunit. A second site is located in the vestibule of the receptor, in a preexisting intrasubunit pocket opposite the agonist binding site and corresponds to a previously identified site involved in positive allosteric modulation of the bacterial homolog ELIC. A third site is located at a pocket right below the agonist binding site. Using electrophysiological recordings on the human α7 nAChR we demonstrate that the identified fragments, which bind at these sites, can modulate receptor activation. This work presents a structural framework for different allosteric binding sites in the α7 nAChR and paves the way for future development of novel allosteric modulators with therapeutic potential.
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