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The Cys-loop ligand-gated ion channel superfamily is composed of the nicotinic acetylcholine receptor (nAChR), 5-HT3 receptor, GABAA receptor (GABAAR), glycine receptor (GlyR), and the zinc-activated ion channel (ZAC). The nAChR, 5-HT3 receptor and ZAC are cation-specific and allow sodium and potassium ions to flow through the pore, generating an excitatory postsynaptic current. However, GlyR and GABAAR are anion-specific and therefore permeable to chloride ions, causing an inhibitory postsynaptic current. All channels in the superfamily are composed of five subunits that form a pentameric arrangement around a central pore. Cys-loop receptors possess a characteristic loop of 13 highly-conserved amino acids flanked by two cysteine (Cys) residues that form a disulfide bond, known as the Cys-loop.

Receptor structure
All members of the Cys-loop superfamily of receptors have a great deal of homology in their secondary and tertiary structures. The elucidation of the crystal structure of the Torpedo marmorata nAChR has provided insights into the structures of other Cys-loop receptors.

Cys-loop receptors have five subunits that form a central pore. All subunits have a large extracellular domain formed by ten β-strands. These interact to form a beta-sandwich. The neurotransmitter binding site is associated with this N-terminal extracellular domain, and strong cation-π interactions are found between the agonist and receptor. The subunits also have a transmembrane domain formed by four alpha helices (M1-M4). The pore is formed by the M2 helices of each of the subunits. There is also an intracellular, amphipathic α-helix known as the MA stretch that is involved in the single channel conductances of both anion- and cation-selective channels.

It has also been shown that the M3-M4 linker is the intracellular domain that binds the cytoskeleton.

Pore structure and gating
The pore is formed by the M2 helices from each of the subunits. In the nAChR, the M2 helices form a V-like structure, which is widest at the extracellular end. The selectivity filter is on the cytoplasmic side of the pore and extends into the M1-M2 cytoplasmic loop and is conserved. The barrier to ion permeability in the closed state is not the occlusion of the pore but rather the hydrophobic barrier that is formed by the "hydrophobic girdle." This hydrophobic girdle consists of rings of hydrophobic amino acid residues lining the interior of the pore.

After neurotransmitter binding, the residues near the binding site open first, and there is a conformational wave which propagates down the transmembrane helices. The conformational change occurs because ligand binding causes rotation of the β-sheets. This rotation displaces two loops found at the interface of the extracellular and transmembrane domains: the Cys-loop and loop 2 (a loop between β-sheets of the extracellular domain). This results in the twisting of the M2 helix, which causes the helices to separate and the hydrophobic girdle to widen, opening the channel.