ArticleProceedings of the National Academy of Sciences of the United States of America2014
Functional differences between neurotransmitter binding sites of muscle acetylcholine receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Article
- Article
- Wrinkle-Improving Effect of Novel Peptide That Binds to Nicotinic Acetylcholine Receptor.International journal of molecular sciences · 2024Article
- Impaired gating of γ- and ε-AChR respectively causes Escobar syndrome and fast-channel myasthenia.Annals of clinical and translational neurology · 2023Article
- Novel Three-Finger Neurotoxins fromToxins · 2021Article
- The Structure, Function, and Physiology of the Fetal and Adult Acetylcholine Receptor in Muscle.Frontiers in molecular neuroscience · 2020Review
- Rapsyn facilitates recovery from desensitization in fetal and adult acetylcholine receptors expressed in a muscle cell line.The Journal of physiology · 2019Article
- Efficiency measures the conversion of agonist binding energy into receptor conformational change.The Journal of general physiology · 2019Article
- A single molecular distance predicts agonist binding energy in nicotinic receptors.The Journal of general physiology · 2019Article
- Cyclic activation of endplate acetylcholine receptors.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Molecular recognition at cholinergic synapses: acetylcholine versus choline.The Journal of physiology · 2017Article
- A mechanism for acetylcholine receptor gating based on structure, coupling, phi, and flip.The Journal of general physiology · 2017Article
- Structural correlates of affinity in fetal versus adult endplate nicotinic receptors.Nature communications · 2016Article
- Host-parasite interaction: multiple sites in the Plasmodium vivax tryptophan-rich antigen PvTRAg38 interact with the erythrocyte receptor band 3.FEBS letters · 2016Article
- Modal affinities of endplate acetylcholine receptors caused by loop C mutations.The Journal of general physiology · 2015Article
- Activation of endplate nicotinic acetylcholine receptors by agonists.Biochemical pharmacology · 2015Review
- Function of the M1 π-helix in endplate receptor activation and desensitization.The Journal of physiology · 2015Article
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Authors and funding
6 authors.
Funding
Abstract
A muscle acetylcholine receptor (AChR) has two neurotransmitter binding sites located in the extracellular domain, at αδ and either αε (adult) or αγ (fetal) subunit interfaces. We used single-channel electrophysiology to measure the effects of mutations of five conserved aromatic residues at each site with regard to their contribution to the difference in free energy of agonist binding to active versus resting receptors (ΔGB1). The two binding sites behave independently in both adult and fetal AChRs. For four different agonists, including ACh and choline, ΔGB1 is ∼-2 kcal/mol more favorable at αγ compared with at αε and αδ. Only three of the aromatics contribute significantly to ΔGB1 at the adult sites (αY190, αY198, and αW149), but all five do so at αγ (as well as αY93 and γW55). γW55 makes a particularly large contribution only at αγ that is coupled energetically to those contributions of some of the α-subunit aromatics. The hydroxyl and benzene groups of loop C residues αY190 and αY198 behave similarly with regard to ΔGB1 at all three kinds of site. ACh binding energies estimated from molecular dynamics simulations are consistent with experimental values from electrophysiology and suggest that the αγ site is more compact, better organized, and less dynamic than αε and αδ. We speculate that the different sensitivities of the fetal αγ site versus the adult αε and αδ sites to choline and ACh are important for the proper maturation and function of the neuromuscular synapse.
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