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Gating of nicotinic ACh receptors; new insights into structural transitions triggered by agonist binding that induce channel opening
Author(s) -
Gay Elaine A.,
Yakel Jerrel L.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.142554
Subject(s) - gating , biophysics , ligand gated ion channel , chemistry , cys loop receptors , nicotinic agonist , ion channel , light gated ion channel , binding site , trpc1 , acetylcholine receptor , agonist , allosteric regulation , protein subunit , nicotinic acetylcholine receptor , salt bridge , receptor , biochemistry , biology , gene , mutant
Nicotinic acetylcholine receptors (nAChRs) are in the superfamily of Cys‐loop ligand‐gated ion channels, and are pentameric assemblies of five subunits, with each subunit arranged around the central ion‐conducting pore. The binding of ACh to the extracellular interface between two subunits induces channel opening. With the recent 4 Å resolution of the Torpedo nAChR, and the crystal structure of the related molluscan ACh binding protein, much has been learned about the structure of the ligand binding domain and the channel pore, as well as major structural rearrangements that may confer channel opening. For example, the putative pathway coupling agonist binding to channel gating may include a major rearrangement of the C‐loop within the ligand binding pocket, and the disruption of a salt bridge between an arginine residue at the end of the β10 strand and a glutamate residue in the β1–β2 linker. Here we will review and discuss the latest structural findings aiming to further refine the transduction pathway linking binding to gating for the nAChR channels, and discuss similarities and differences among the different members of this Cys‐loop superfamily of receptors.