ArticleScientific reports2017
Structural mechanisms for α-conotoxin activity at the human α3β4 nicotinic acetylcholine receptor.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Article
- Computational Design of α-Conotoxins to Target Specific Nicotinic Acetylcholine Receptor Subtypes.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders.Journal of medicinal chemistry · 2023Review
- Unravelling the allosteric binding mode of αD-VxXXB at nicotinic acetylcholine receptors.Frontiers in pharmacology · 2023Article
- Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications.Biomolecules · 2022Review
- Posttranslational modifications of α-conotoxins: sulfotyrosine and C-terminal amidation stabilise structures and increase acetylcholine receptor binding.RSC medicinal chemistry · 2021Article
- Characterization of an α 4/7-Conotoxin LvIF fromMarine drugs · 2021Article
- Potency- and Selectivity-Enhancing Mutations of Conotoxins for Nicotinic Acetylcholine Receptors Can Be Predicted Using Accurate Free-Energy Calculations.Marine drugs · 2021Article
- An Investigation of Three-Finger Toxin-nAChR Interactions through Rosetta Protein Docking.Toxins · 2020Article
- Article
- Interactions of the α3β2 Nicotinic Acetylcholine Receptor Interfaces with α-Conotoxin LsIA and its Carboxylated C-terminus Analogue: Molecular Dynamics Simulations.Marine drugs · 2020Article
- Structure-Function of Neuronal Nicotinic Acetylcholine Receptor Inhibitors Derived From Natural Toxins.Frontiers in neuroscience · 2020Review
- ConoMode, a database for conopeptide binding modes.Database : the journal of biological databases and curation · 2020Article
- Effects of C-Terminal Carboxylation on α-Conotoxin LsIA Interactions with Human α7 Nicotinic Acetylcholine Receptor: Molecular Simulation Studies.Marine drugs · 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
- Neuronal Nicotinic Acetylcholine Receptor Modulators from Cone Snails.Marine drugs · 2018Review
- α-Conotoxins active at α3-containing nicotinic acetylcholine receptors and their molecular determinants for selective inhibition.British journal of pharmacology · 2018Review
- Review
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6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Nicotinic acetylcholine receptors (nAChR) are therapeutic targets for a range of human diseases. α-Conotoxins are naturally occurring peptide antagonists of nAChRs that have been used as pharmacological probes and investigated as drug leads for nAChR related disorders. However, α-conotoxin interactions have been mostly characterised at the α7 and α3β2 nAChRs, with interactions at other subtypes poorly understood. This study provides novel structural insights into the molecular basis for α-conotoxin activity at α3β4 nAChR, a therapeutic target where subtype specific antagonists have potential to treat nicotine addiction and lung cancer. A co-crystal structure of α-conotoxin LsIA with Lymnaea stagnalis acetylcholine binding protein guided the design and functional characterisations of LsIA analogues that identified the minimum pharmacophore regulating α3β4 antagonism. Interactions of the LsIA R10F with β4 K57 and the conserved -NN- α-conotoxin motif with β4 I77 and I109 conferred α3β4 activity to the otherwise inactive LsIA. Using these structural insights, we designed LsIA analogues with α3β4 activity. This new understanding of the structural basis of protein-protein interactions between α-conotoxins and α3β4 may help rationally guide the development of α3β4 selective antagonists with therapeutic potential.
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