ArticleThe Journal of physiology2011
Cysteine modification reveals which subunits form the ligand binding site in human heteromeric 5-HT3AB receptors.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- The serotonin-gated 5-HT3 receptor: a tale of functions and structures of a prototypical pentameric ligand-gated ion channel.Acta pharmacologica Sinica · 2026Review
- Mutations of the nACh Receptor M4 Helix Reveal Different Phenotypes in Different Expression Systems: Could Lipids be Responsible?Frontiers in physiology · 2022Article
- Tapping into 5-HTInternational journal of molecular sciences · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Structure, Function and Physiology of 5-Hydroxytryptamine Receptors Subtype 3.Sub-cellular biochemistry · 2021Review
- The binding orientations of structurally-related ligands can differ; A cautionary note.Neuropharmacology · 2017Article
- Novel mechanism of modulation at a ligand-gated ion channel; action of 5-Cl-indole at the 5-HTBritish journal of pharmacology · 2016Article
- 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous Systems.ACS chemical neuroscience · 2015Article
- Allosteric activation of the 5-HT3AB receptor by mCPBG.Neuropharmacology · 2015Article
- The binding characteristics and orientation of a novel radioligand with distinct properties at 5-HT3A and 5-HT3AB receptors.Neuropharmacology · 2014Article
- The Concise Guide to PHARMACOLOGY 2013/14: ligand-gated ion channels.British journal of pharmacology · 2013Article
- Exploring a potential palonosetron allosteric binding site in the 5-HT(3) receptor.Bioorganic & medicinal chemistry · 2013Article
- Agonists and antagonists induce different palonosetron dissociation rates in 5-HT₃A and 5-HT₃AB receptors.Neuropharmacology · 2013Article
- A single channel mutation alters agonist efficacy at 5-HT3A and 5-HT3AB receptors.British journal of pharmacology · 2013Article
- The 5-HT3AB receptor shows an A3B2 stoichiometry at the plasma membrane.Biophysical journal · 2013Article
- Prolonged inhibition of 5-HT₃ receptors by palonosetron results from surface receptor inhibition rather than inducing receptor internalization.British journal of pharmacology · 2013Article
- Approaching the 5-HT₃ receptor heterogeneity by computational studies of the transmembrane and intracellular domains.Journal of computer-aided molecular design · 2013Article
- Structure-activity relationships of quinoxaline-based 5-HT3A and 5-HT3AB receptor-selective ligands.ChemMedChem · 2013Article
- Discriminating between 5-HT₃A and 5-HT₃AB receptors.British journal of pharmacology · 2013Review
- Bacterially expressed human serotonin receptor 3A is functionally reconstituted in proteoliposomes.Protein expression and purification · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The ligand binding site of Cys-loop receptors is formed by residues on the principal (+) and complementary (-) faces of adjacent subunits, but the subunits that constitute the binding pocket in many heteromeric receptors are not yet clear. To probe the subunits involved in ligand binding in heteromeric human 5-HT(3)AB receptors, we made cysteine substitutions to the + and - faces of A and B subunits, and measured their functional consequences in receptors expressed in Xenopus oocytes. All A subunit mutations altered or eliminated function. The same pattern of changes was seen at homomeric and heteromeric receptors containing cysteine substitutions at A(R92) (- face), A(L126)(+), A(N128)(+), A(I139)(-), A(Q151)(-) and A(T181)(+), and these receptors displayed further changes when the sulphydryl modifying reagent methanethiosulfonate-ethylammonium (MTSEA) was applied. Modifications of A(R92C)(-)- and A(T181C)(+)-containing receptors were protected by the presence of agonist (5-HT) or antagonist (d-tubocurarine). In contrast modifications of the equivalent B subunit residues did not alter heteromeric receptor function. In addition a double mutant, A(S206C)(-)(/E229C)(+), only responded to 5-HT following DTT treatment in both homomeric and heteromeric receptors, indicating receptor function was inhibited by a disulphide bond between an A+ and an A- interface in both receptor types. Our results are consistent with binding to an A+A- interface at both homomeric and heteromeric human 5-HT(3) receptors, and explain why the competitive pharmacologies of these two receptors are identical.
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Registered trials
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.