Cys-loop receptors
Encyclopedia
The Cys-loop ligand-gated ion channel
superfamily is composed of nicotinic acetylcholine
, GABAA
, GABAA-ρ, glycine
and 5-HT3 receptors
that are composed of five protein subunit
s that form a pentameric arrangement around a central pore. There are usually 2 alpha subunits and 3 other beta, gamma, or delta subunits (some consist of 5 alpha subunits). Cys-loop receptors possess a characteristic loop formed by a disulfide bond between two cysteine
(Cys) residues 13 highly conserved amino acids apart near the N-terminal extracellular domain of the alpha subunit.
All subunits consist of a conserved extracellular large N-terminal domain, three highly conserved transmembrane domains, a cytoplasmic loop of variable size and amino acid sequence, and a fourth transmembrane domain with a relatively short and variable extracellular C terminal. All alpha subunits have a characteristic cys-cys pair in the N-terminal extracellular domain, this is shown to be essential for agonist binding.
The neurotransmitter
s bind at the interface between subunits in the extracellular domain.
Each subunit contains 4-membrane-spanning alpha helixes (M1, M2, M3, M4). The pore is formed primarily by M2 of the two alpha subunits.
The M3-M4 linker is the intracellular domain that binds the cytoskeleton.
Ligand-gated ion channel
Ligand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger , such as a neurotransmitter.The binding site of endogenous ligands on LGICs...
superfamily is composed of nicotinic acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
, GABAA
GABA A receptor
The GABAA receptor is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid , the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in...
, GABAA-ρ, glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
and 5-HT3 receptors
5-HT3 receptor
The 5-HT3 receptor is a member of the superfamily of ligand-gated ion channels, a superfamily that also includes the neuronal nicotinic acetylcholine receptors , and the inhibitory neurotransmitter receptors for GABA and glycine...
that are composed of five protein subunit
Protein subunit
In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...
s that form a pentameric arrangement around a central pore. There are usually 2 alpha subunits and 3 other beta, gamma, or delta subunits (some consist of 5 alpha subunits). Cys-loop receptors possess a characteristic loop formed by a disulfide bond between two cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
(Cys) residues 13 highly conserved amino acids apart near the N-terminal extracellular domain of the alpha subunit.
All subunits consist of a conserved extracellular large N-terminal domain, three highly conserved transmembrane domains, a cytoplasmic loop of variable size and amino acid sequence, and a fourth transmembrane domain with a relatively short and variable extracellular C terminal. All alpha subunits have a characteristic cys-cys pair in the N-terminal extracellular domain, this is shown to be essential for agonist binding.
The neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s bind at the interface between subunits in the extracellular domain.
Each subunit contains 4-membrane-spanning alpha helixes (M1, M2, M3, M4). The pore is formed primarily by M2 of the two alpha subunits.
The M3-M4 linker is the intracellular domain that binds the cytoskeleton.