ArticleThe Journal of biological chemistry2009
Aromatic Residues {epsilon}Trp-55 and {delta}Trp-57 and the Activation of Acetylcholine Receptor Channels.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Structural correlates of affinity in fetal versus adult endplate nicotinic receptors.Nature communications · 2016Article
- Agonist activation of a nicotinic acetylcholine receptor.Neuropharmacology · 2015Review
- Functional differences between neurotransmitter binding sites of muscle acetylcholine receptors.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Catch-and-hold activation of muscle acetylcholine receptors having transmitter binding site mutations.Biophysical journal · 2014Article
- α1F64 Residue at GABA(A) receptor binding site is involved in gating by influencing the receptor flipping transitions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Function of interfacial prolines at the transmitter-binding sites of the neuromuscular acetylcholine receptor.The Journal of biological chemistry · 2013Article
- Highly fatal fast-channel syndrome caused by AChR ε subunit mutation at the agonist binding site.Neurology · 2012Article
- An integrated catch-and-hold mechanism activates nicotinic acetylcholine receptors.The Journal of general physiology · 2012Article
- Sources of energy for gating by neurotransmitters in acetylcholine receptor channels.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Mapping the sequence of conformational changes underlying selectivity filter gating in the K(v)11.1 potassium channel.Nature structural & molecular biology · 2011Article
- Molecular determinants for competitive inhibition of alpha4beta2 nicotinic acetylcholine receptors.Molecular pharmacology · 2010Article
- Acetylcholine receptor channels activated by a single agonist molecule.Biophysical journal · 2010Article
- Energetics of gating at the apo-acetylcholine receptor transmitter binding site.The Journal of general physiology · 2010Article
- The gating isomerization of neuromuscular acetylcholine receptors.The Journal of physiology · 2010Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The two transmitter binding sites of the neuromuscular acetylcholine (ACh) receptor channel contain several aromatic residues, including a tryptophan located on the complementary, negative face of each binding pocket. These two residues, Trp-55 in the epsilon subunit and Trp-57 in the delta subunit, were mutated (AEFHILRVY), and for most constructs the rate constants for acetylcholine binding and channel gating were estimated by using single channel kinetic analyses. The rate constants for unliganded channel opening and closing were also estimated for some mutants. From these measurements we calculated all of the equilibrium constants of the "allosteric" cycle as follows: diliganded gating, unliganded gating, dissociation from the C(losed) conformation, and dissociation from the O(pen) conformation. The results indicate the following. (i) These aromatic side chains play a relatively minor role in ACh receptor channel activation. (ii) The main consequence of mutations is to reduce the affinity of the O conformation of the binding site for ACh, with the effect being greater at the epsilon subunit. (iii) In epsilon (but not delta) the aromatic nature of the side chain is important in determining affinity, to a slightly greater degree in the O conformation. Phi value analyses (of both tryptophan residues) show Phi approximately 1 for both the ACh binding and diliganded gating reactions. (iv) This suggests that the structural boundaries of the dynamic elements of the gating conformational change may not be subunit-delimited, and (v) the mutated tryptophan residues experience energy changes that occur relatively early in both the ligand-binding and channel-gating reactions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.