Cys-loop receptor

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 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 neurotransmitters bind at the interface between subunits in the extracellular domain.

Each subunit contains 4-membrane-spanning alpha helices (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.

See also

• Ion channel
• Nicotinic agonists
• Receptor (biochemistry)

References

• Van Arnam, EB, Dougherty, DA (August 14, 2014). "Functional probes of drug-receptor interactions implicated by structural studies: cys-loop receptors provide a fertile testing ground". Journal of Medicinal Chemistry (57): 6289–6300. doi:10.1021/jm500023m. PMC 4136689.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: multiple names: authors list (link)
• Bourne, Y; et al. (October 19, 2005). "Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations". The EMBO Journal (24(20)): 3635–3646. doi:10.1038/sj.emboj.7600828. PMC 1276711. {{cite journal}}: Explicit use of et al. in: |last1= (help)CS1 maint: PMC format (link)
• Huang, Y, Zhang, JL, Wu, W, Chang, YC (June 2009). "Allosteric activation mechanism of the cys-loop receptors". Acta Pharmacologica Sinica (30(6)): 663–672. doi:10.1038/aps.2009.51. PMC 19444220. {{cite journal}}: Check |pmc= value (help)CS1 maint: multiple names: authors list (link)
• Yakel, J (February 15, 2010). "Advances and hold-ups in the study of structure, function and regulation of cys-loop ligand-gated ion channels and receptors". The Journal of Physiology (588 (Pt. 4)): 555–556. doi:10.1113/jphysiol.2009.185488. PMC 2828129.{{cite journal}}: CS1 maint: PMC format (link)
• Pless, SA, Lynagh, T (April 24, 2014). "Principles of agonist recognition in Cys-loop receptors". Frontiers in Physiology (5): 160. doi:10.3389/fphys.2014.00160. PMC 4006026.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
• 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; et al. (2009). "Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function". Physiol Rev. 89 (1): 73–120. doi:10.1152/physrev.00015.2008. PMC 2713585. PMID 19126755.

External links

• Overview at gwumc.edu