Open AccessThe Emerging Three‐Dimensional Structure of a Receptor
Author(s) -
Hucho Ferdinand,
Tsetlin Victor I.,
Machold Jan
Publication year - 1996
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1996.0539u.x
Subject(s) - nicotinic acetylcholine receptor , ion channel , competitive antagonist , binding site , biophysics , ligand gated ion channel , acetylcholine receptor , helix (gastropod) , torpedo , cys loop receptors , nicotinic agonist , agonist , chemistry , biology , receptor , biochemistry , ecology , snail
The nicotinic acetylcholine receptor is the neurotransmitter receptor with the most‐characterized protein structure. The amino acid sequences of its five subunits have been elucidated by cDNA cloning and sequencing. Its shape and dimensions (approximately 12.5 nm×8 nm) were deduced from electron‐microscopy studies. Its subunits are arranged around a five‐fold axis of pseudosymmetry in the order (clockwise) α H γα L δβ. Its two agonist/competitive‐antagonist‐binding sites have been localized by photola‐belling studies to a deep gorge between the subunits near the membrane surface. Its ion channel is formed by five membrane‐spanning (M2) helices that are contributed by the five subunits. This finding has been generalized as the Helix M2 model for the superfamily of ligand‐gated ion channels. The binding site for regulatory non‐competitive antagonists has been localized by photolabelling and site‐directed‐mutagenesis studies within this ion channel. Therefore a three‐dimensional image of the nicotinic acetylcholine receptor is emerging, the most prominent feature of which is an active site that combines the agonist/competitive‐antagonist‐binding sites, the regulatory site and the ion channel within a relatively narrow space close to and within the bilayer membrane.