S
IPR018000

Neurotransmitter-gated ion-channel, conserved site

InterPro entry
Short nameNeurotransmitter_ion_chnl_CS

Description

This entry represents a conserved site based around two highly conserved cysteines in the N-terminal of AchR/GABA/5HT3/Gly receptors. The residues between these two cysteines are also well conserved. In AchR, these cysteine residues have been shown to form a disulphide bond essential to the tertiary structure of the receptor.

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
[3, 4]
. 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
[7]
.
 * Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits
[5]
.
 * Gamma-aminobutyric acid (GABA) receptor, an inhibitory chloride ion channel; at least four types of subunits (alpha, beta, gamma and delta) are known
[6]
.
 * Serotonin 5HT3 receptor, of which there are seven major types (5HT3-5HT7)
[1]
.
 * Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate)
[2]
.


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
[3, 4]
.

References

1.Structural features of the ligand-binding domain of the serotonin 5HT3 receptor. Yan D, Schulte MK, Bloom KE, White MM. J. Biol. Chem. 274, 5537-41, (1999). View articlePMID: 10026168

2.Structure and gating of the glutamate receptor ion channel. Wollmuth LP, Sobolevsky AI. Trends Neurosci. 27, 321-8, (2004). View articlePMID: 15165736

3.Determination of the tyrosine phosphorylation sites of the nicotinic acetylcholine receptor. Wagner K, Edson K, Heginbotham L, Post M, Huganir RL, Czernik AJ. J. Biol. Chem. 266, 23784-9, (1991). View articlePMID: 1721053

4.Generation of two forms of the gamma-aminobutyric acidA receptor gamma 2-subunit in mice by alternative splicing. Kofuji P, Wang JB, Moss SJ, Huganir RL, Burt DR. J. Neurochem. 56, 713-5, (1991). View articlePMID: 1846404

5.Molecular structure and function of the glycine receptor chloride channel. Lynch JW. Physiol. Rev. 84, 1051-95, (2004). PMID: 15383648

6.GABA(A) receptors: Subtypes provide diversity of function and pharmacology. Olsen RW, Sieghart W. Neuropharmacology (2008). PMID: 18760291

7.Assembly and trafficking of nicotinic acetylcholine receptors (Review). Millar NS, Harkness PC. Mol. Membr. Biol. 25, 279-92, (2008). View articlePMID: 18446614

Cross References

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