InterPro domain: IPR036719

Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses [ 1 , 2 ]. Five of these ion channel receptor families have been shown to form a sequence-related superfamily:

• Nicotinic acetylcholine receptor (AchR), an excitatory cation channel in vertebrates and invertebrates; in vertebrate motor endplates it is composed of alpha, beta, gamma and delta/epsilon subunits; in neurons it is composed of alpha and non-alpha (or beta) subunits [ 3 ].
• Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits [ 4 ].
• Gamma-aminobutyric acid (GABA) receptor, an inhibitory chloride ion channel; at least four types of subunits (alpha, beta, gamma and delta) are known [ 5 ].
• Serotonin 5HT3 receptor, of which there are seven major types (5HT3-5HT7) [ 6 ].
• Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate) [ 7 ].

These receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. A fourth hydrophobic region is found at the C-terminal of the sequence [ 8 , 8 ].

This domain represents four transmembrane helices of a variety of neurotransmitter-gated ion-channels.

1. Determination of the tyrosine phosphorylation sites of the nicotinic acetylcholine receptor. J. Biol. Chem. 266, 23784-9
2. Generation of two forms of the gamma-aminobutyric acidA receptor gamma 2-subunit in mice by alternative splicing. J. Neurochem. 56, 713-5
3. Assembly and trafficking of nicotinic acetylcholine receptors (Review). Mol. Membr. Biol. 25, 279-92
4. Molecular structure and function of the glycine receptor chloride channel. Physiol. Rev. 84, 1051-95
5. GABA(A) receptors: Subtypes provide diversity of function and pharmacology. Neuropharmacology 27, 321-8
6. Structural features of the ligand-binding domain of the serotonin 5HT3 receptor. J. Biol. Chem. 274, 5537-41
7. Structure and gating of the glutamate receptor ion channel. Trends Neurosci.