Cys-loop receptor

The Cys-loop ligand-gated ion channel superfamily is composed of nicotinic acetylcholine, GABAA, GABAA-ρ, glycine, 5-HT3, and zinc-activated (ZAC) receptors. These receptors 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). The name of the family refers to a characteristic loop formed by 13 highly conserved amino acids between two cysteine (Cys) residues, which form a disulfide bond[1] near the N-terminal extracellular domain.

Cys-loop receptors are known only in eukaryotes, but are part of a larger family of pentameric ligand-gated ion channels. Only the Cys-loop clade includes the pair of bridging cysteine residues.[2] The larger superfamily includes bacterial (e.g. GLIC) as well as non-Cys-loop eukaryotic receptors, and is referred to as "pentameric ligand-gated ion channels", or "Pro-loop receptors".[3]

All subunits consist of a large conserved extracellular N-terminal domain, three highly conserved transmembrane domains, a cytoplasmic loop of variable size and amino acid sequence, and a fourth transmembrane region with a relatively short and variable extracellular C-terminal domain. Neurotransmitters bind at the interface between subunits in the extracellular domain.

Each subunit contains four membrane-spanning alpha helices (M1, M2, M3, M4). The pore is formed primarily by the M2 helices.[4] The M3-M4 linker is the intracellular domain that binds the cytoskeleton.

  1. ^ Kellaris, Kennan Vincent (Apr 18, 1989). "Assessment of the number of free cysteines and isolation and identification of cystine-containing peptides from acetylcholine receptor". Biochemistry. 28 (8): 3469–3482. doi:10.1021/bi00434a048. PMID 2742850. Retrieved 3 February 2021.
  2. ^ Tasneem A, Iyer L, Jakobsson E, Aravind L (2004). "Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels". Genome Biology. 6 (1): R4. doi:10.1186/gb-2004-6-1-r4. PMC 549065. PMID 15642096.
  3. ^ Jaiteh M, Taly A, Hénin J (2016). "Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors". PLOS ONE. 11 (3): e0151934. Bibcode:2016PLoSO..1151934J. doi:10.1371/journal.pone.0151934. PMC 4795631. PMID 26986966.
  4. ^ Sine S; Engel A (2006). "Recent advances in Cys-loop receptor structure and function". Nature. 440 (7083): 448–55. Bibcode:2006Natur.440..448S. doi:10.1038/nature04708. PMID 16554804. S2CID 3899722.