ArticleThe Journal of biological chemistry2018
An allosteric binding site of the α7 nicotinic acetylcholine receptor revealed in a humanized acetylcholine-binding protein.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Chimeric Approach to Identify Molecular Determinants of Nicotinic Acetylcholine Receptors.International journal of molecular sciences · 2026Review
- Glutamine synthetase in astrocytes of the caudate and putamen is responsible for locomotor sensitization after nicotine exposure.Acta pharmaceutica Sinica. B · 2025Article
- A workflow to create a high-quality protein-ligand binding dataset for training, validation, and prediction tasks.Digital discovery · 2025Article
- Article
- Inhibition of NMDA receptors and other ion channel types by membrane-associated drugs.Frontiers in pharmacology · 2025Review
- Efficient Expression inMolecules (Basel, Switzerland) · 2024Article
- Comparison of Conformations and Interactions with Nicotinic Acetylcholine Receptors forInternational journal of molecular sciences · 2023Article
- An original potentiating mechanism revealed by the cryo-EM structures of the human α7 nicotinic receptor in complex with nanobodies.Nature communications · 2023Article
- Generation of nanobodies acting as silent and positive allosteric modulators of the α7 nicotinic acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2023Article
- Unravelling the allosteric binding mode of αD-VxXXB at nicotinic acetylcholine receptors.Frontiers in pharmacology · 2023Article
- Synthesis of full-length homodimer αD-VxXXB that targets human α7 nicotinic acetylcholine receptors.RSC medicinal chemistry · 2022Article
- Delineating the activity of the potent nicotinic acetylcholine receptor agonists (+)-anatoxin-a and (-)-hosieine-A.Acta crystallographica. Section F, Structural biology communications · 2022Article
- A computational study on hydroxychloroquine binding to target proteins related to SARS-COV-2 infection.Informatics in medicine unlocked · 2021Article
- Multidimensional Intersection of Nicotine, Gene Expression, and Behavior.Frontiers in behavioral neuroscience · 2021Article
- 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
- Progress in nicotinic receptor structural biology.Neuropharmacology · 2020Review
- Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.Neuropharmacology · 2020Review
- Modulation of theeLife · 2020Article
- Cloning and Expression of Cockroach α7 Nicotinic Acetylcholine Receptor Subunit.Frontiers in physiology · 2020Article
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nicotinic acetylcholine receptors (nAChRs) belong to the family of pentameric ligand-gated ion channels and mediate fast excitatory transmission in the central and peripheral nervous systems. Among the different existing receptor subtypes, the homomeric α7 nAChR has attracted considerable attention because of its possible implication in several neurological and psychiatric disorders, including cognitive decline associated with Alzheimer's disease or schizophrenia. Allosteric modulators of ligand-gated ion channels are of particular interest as therapeutic agents, as they modulate receptor activity without affecting normal fluctuations of synaptic neurotransmitter release. Here, we used X-ray crystallography and surface plasmon resonance spectroscopy of α7-acetylcholine-binding protein (AChBP), a humanized chimera of a snail AChBP, which has 71% sequence similarity with the extracellular ligand-binding domain of the human α7 nAChR, to investigate the structural determinants of allosteric modulation. We extended previous observations that an allosteric site located in the vestibule of the receptor offers an attractive target for receptor modulation. We introduced seven additional humanizing mutations in the vestibule-located binding site of AChBP to improve its suitability as a model for studying allosteric binding. Using a fragment-based screening approach, we uncovered an allosteric binding site located near the β8-β9 loop, which critically contributes to coupling ligand binding to channel opening in human α7 nAChR. This work expands our understanding of the topology of allosteric binding sites in AChBP and, by extrapolation, in the human α7 nAChR as determined by electrophysiology measurements. Our insights pave the way for drug design strategies targeting nAChRs involved in ion channel-mediated disorders.
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