Cys-loop receptors

The Cys-loop ligand-gated ion channel superfamily is composed of nicotinic acetylcholine, GABA_A, GABA_A-ρ, glycine and 5-HT₃ receptors that are composed of five protein subunits which 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 neurotransmitters 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 primarily formed by M2 of the two alpha subunits.

The M3-M4 linker is the intracellular domain that binds the cytoskeleton.

References

• Sine S, Engel A (2006). "Recent advances in Cys-loop receptor structure and function". Nature. 440 (7083): 448–55. doi:10.1038/nature04708. PMID 16554804. 
• Albuquerque; Pereira, EF; Alkondon, M; Rogers, SW; et al. (2009). "Mammalian Nicotinic Acetylcholine Receptors: from Structure to Function". Physiol Rev. 89 (89): 73–120. doi:10.1152/physrev.00015.2008. PMC 2713585 Freely accessible. PMID 19126755. CS1 maint: Explicit use of et al. (link)

See also

• ion channel
• Nicotinic agonists
• Receptor (biochemistry)

External links

• Overview at gwumc.edu