ArticleBiophysical journal2009
Long-range coupling in an allosteric receptor revealed by mutant cycle analysis.
Article in Biophysical journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Identification, characterization, and structure-activity relationship of the ASIC3-selective peptide WRPRFa.Communications chemistry · 2025Article
- Intrasubunit and Intersubunit Steroid Binding Sites Independently and Additively MediateMolecular pharmacology · 2021Article
- Identifying coupled clusters of allostery participants through chemical shift perturbations.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Lynx Prototoxins: Roles of Endogenous Mammalian Neurotoxin-Like Proteins in Modulating Nicotinic Acetylcholine Receptor Function to Influence Complex Biological Processes.Frontiers in pharmacology · 2019Review
- A triad of residues is functionally transferrable between 5-HTThe Journal of biological chemistry · 2018Article
- Differential Contribution of Subunit Interfaces to α9α10 Nicotinic Acetylcholine Receptor Function.Molecular pharmacology · 2017Article
- Heterologous expression and nonsense suppression provide insights into agonist behavior at α6β2 nicotinic acetylcholine receptors.Neuropharmacology · 2015Article
- An Unaltered Orthosteric Site and a Network of Long-Range Allosteric Interactions for PNU-120596 in α7 Nicotinic Acetylcholine Receptors.Chemistry & biology · 2015Article
- Subunit interfaces contribute differently to activation and allosteric modulation of neuronal nicotinic acetylcholine receptors.Neuropharmacology · 2015Article
- A self-consistent approach for determining pairwise interactions that underlie channel activation.The Journal of general physiology · 2014Article
- NbIT--a new information theory-based analysis of allosteric mechanisms reveals residues that underlie function in the leucine transporter LeuT.PLoS computational biology · 2014Article
- Probing the non-canonical interface for agonist interaction with an α5 containing nicotinic acetylcholine receptor.Neuropharmacology · 2014Article
- Propofol modulation of α1 glycine receptors does not require a structural transition at adjacent subunits that is crucial to agonist-induced activation.ACS chemical neuroscience · 2013Article
- An engineered glutamate-gated chloride (GluCl) channel for sensitive, consistent neuronal silencing by ivermectin.The Journal of biological chemistry · 2013Article
- Binding interactions with the complementary subunit of nicotinic receptors.The Journal of biological chemistry · 2013Article
- Free-energy relationships in ion channels activated by voltage and ligand.The Journal of general physiology · 2013Article
- A coupled array of noncovalent interactions impacts the function of the 5-HT3A serotonin receptor in an agonist-specific way.ACS chemical neuroscience · 2012Article
- Gating movement of acetylcholine receptor caught by plunge-freezing.Journal of molecular biology · 2012Article
- Using mutant cycle analysis to elucidate long-range functional coupling in allosteric receptors.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Blockade of neuronal α7-nAChR by α-conotoxin ImI explained by computational scanning and energy calculations.PLoS computational biology · 2011Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The functional coupling of residues that are far apart in space is the quintessential property of allosteric proteins. For example, in Cys-loop receptors, the gating of an intrinsic ion channel is allosterically regulated by the binding of small molecule neurotransmitters 50-60 A from the channel gate. Some residues near the binding site must have as their primary function the communication of the binding event to the gating region. These gating pathway residues are essential to function, but their identification and characterization can be challenging. This work introduces a simple strategy, derived from mutant cycle analysis, for identifying gating pathway residues using macroscopic measurements alone. In the exemplar Cys-loop receptor, the nicotinic acetylcholine receptor, a well-characterized reporter mutation (betaL9'S) known to impact gating, was combined with mutations of target residues in the ligand-binding domain hypothesized or previously found to be functionally significant. A mutant cycle analysis of the macroscopic EC(50) measurements can then provide insights into the role of the target residue. This new method, elucidating long-range functional coupling in allosteric receptors, can be applied to several reporter mutations in a wide variety of receptors to identify previously characterized and novel mutations that impact the gating pathway. We support our interpretation of macroscopic data with single-channel studies. Elucidating long-range functional coupling in allosteric receptors should be broadly applicable to determining functional roles of residues in allosteric receptors.
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