The molecular basis of the structure and function of the 5-HT 3 receptor: a model ligand-gated ion channel (Review)

  title={The molecular basis of the structure and function of the 5-HT 3 receptor: a model ligand-gated ion channel (Review)},
  author={David C. Reeves and Sarah C. R. Lummis},
  journal={Molecular Membrane Biology},
  pages={11 - 26}
The ligand-gated ion channel superfamily of neurotransmitter receptors are proteins responsible for rapid transmission of nerve impulses at the synapse and have, therefore, been the subject of intensive research for many years. The cys-loop family, of which the 5-HT3 receptor is a member, includes the nicotinic acetylcholine receptor, the GABAA receptor and the glycine receptor. A diverse range of endogenous and artificial ligands activate these receptors, but, nevertheless, the family shares… 
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Novel structural determinants of single-channel conductance in nicotinic acetylcholine and 5-hydroxytryptamine type-3 receptors.
Observations from lines of evidence extended to a representative neuronal nicotinic ACh receptor composed of alpha4 and beta2 subunits and, by inference, probably other members of the Cys-loop family are described.


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The analysis of the three-dimensional model allows one to distinguish among amino acids that exert key roles in ligand interactions, subunit architecture, receptor assembly and receptor dynamics, and alternative roles with respect to the ones hypothesized by experimentalists are assigned.
Analysis of the Ligand Binding Site of the 5-HT3 Receptor Using Site Directed Mutagenesis: Importance of Glutamate 106
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors
The crystal structure of molluscan acetylcholine-binding protein (AChBP), a structural and functional homologue of the amino-terminal ligand-binding domain of an nAChR α-subunit, is presented and is relevant for the development of drugs against Alzheimer’s disease and nicotine addiction.
Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel.
A complementary DNA clone containing the coding sequence of one of these rapidly responding channels, a 5HT3 subtype of the serotonin receptor, has been isolated by screening a neuroblastoma expression library for functional expression of serotonin-gated currents in Xenopus oocytes.
Conversion of the ion selectivity of the 5-HT(3a) receptor from cationic to anionic reveals a conserved feature of the ligand-gated ion channel superfamily.
A set of mutations were identified that convert the ion selectivity of the 5-HT(3A) receptor from cationic to anionic; these were substitution of V13'T in M2 together with neutralization of glutamate residues (E-1'A) and the adjacent insertion of a proline residue (P-1') in the M1-M2 loop.
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This work has identified a set of mutations that convert the ion selectivity of the 5-HT3Areceptor from cationic to anionic; these were substitution of V13′T in M2 together with neutralization of glutamate residues (E−1′A) and the adjacent insertion of a proline residue (P− 1′) in the M1-M2 loop.
Evolutionary history of the ligand-gated ion-channel superfamily of receptors
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Data provide direct molecular evidence that the nicotinic α4 subunit co-assembles with the 5-HT3R subunit and forms an integral part of the ion channel pore.