ArticleThe Journal of biological chemistry2011
Crystal structures of a cysteine-modified mutant in loop D of acetylcholine-binding protein.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Enhanced meta-analysis of acetylcholine binding protein structures reveals conformational signatures of agonism in nicotinic receptors.Protein science : a publication of the Protein Society · 2012Pooled it
- Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway.Science advances · 2022Article
- A Functional Interaction Between Y674-R685 Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor.Molecular neurobiology · 2022Article
- Ion Channels in Anesthesia.Advances in experimental medicine and biology · 2021Article
- The Glycine Receptor Allosteric Ligands Library (GRALL).Bioinformatics (Oxford, England) · 2020Article
- Atomistic insights into human Cys-loop receptors by solution NMR.Biochimica et biophysica acta · 2015Article
- Non-equivalent ligand selectivity of agonist sites in (α4β2)2α4 nicotinic acetylcholine receptors: a key determinant of agonist efficacy.The Journal of biological chemistry · 2014Article
- Structural basis for cooperative interactions of substituted 2-aminopyrimidines with the acetylcholine binding protein.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Article
- Identifying key amino acid residues that affect α-conotoxin AuIB inhibition of α3β4 nicotinic acetylcholine receptors.The Journal of biological chemistry · 2013Article
- Glycine receptor mouse mutants: model systems for human hyperekplexia.British journal of pharmacology · 2013Review
- Cholinergic receptors: functional role of nicotinic ACh receptors in brain circuits and disease.Pflugers Archiv : European journal of physiology · 2013Review
- Structural basis for ion permeation mechanism in pentameric ligand-gated ion channels.The EMBO journal · 2013Article
- Partial activation of α7 nicotinic acetylcholine receptors: insights from molecular dynamics simulations.Journal of molecular modeling · 2013Article
- Assembly of a π-π stack of ligands in the binding site of an acetylcholine-binding protein.Nature communications · 2013Article
- Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Size matters in activation/inhibition of ligand-gated ion channels.Trends in pharmacological sciences · 2012Review
- An integrated catch-and-hold mechanism activates nicotinic acetylcholine receptors.The Journal of general physiology · 2012Article
- Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine.Nature communications · 2012Article
- The TM2 6' position of GABA(A) receptors mediates alcohol inhibition.The Journal of pharmacology and experimental therapeutics · 2012Article
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Authors and funding
12 authors at 6 institutions in 5 countries.
Funding
Abstract
Covalent modification of α7 W55C nicotinic acetylcholine receptors (nAChR) with the cysteine-modifying reagent [2-(trimethylammonium)ethyl] methanethiosulfonate (MTSET(+)) produces receptors that are unresponsive to acetylcholine, whereas methyl methanethiolsulfonate (MMTS) produces enhanced acetylcholine-gated currents. Here, we investigate structural changes that underlie the opposite effects of MTSET(+) and MMTS using acetylcholine-binding protein (AChBP), a homolog of the extracellular domain of the nAChR. Crystal structures of Y53C AChBP show that MTSET(+)-modification stabilizes loop C in an extended conformation that resembles the antagonist-bound state, which parallels our observation that MTSET(+) produces unresponsive W55C nAChRs. The MMTS-modified mutant in complex with acetylcholine is characterized by a contracted C-loop, similar to other agonist-bound complexes. Surprisingly, we find two acetylcholine molecules bound in the ligand-binding site, which might explain the potentiating effect of MMTS modification in W55C nAChRs. Unexpectedly, we observed in the MMTS-Y53C structure that ten phosphate ions arranged in two rings at adjacent sites are bound in the vestibule of AChBP. We mutated homologous residues in the vestibule of α1 GlyR and observed a reduction in the single channel conductance, suggesting a role of this site in ion permeation. Taken together, our results demonstrate that targeted modification of a conserved aromatic residue in loop D is sufficient for a conformational switch of AChBP and that a defined region in the vestibule of the extracellular domain contributes to ion conduction in anion-selective Cys-loop receptors.
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