Structural organization of the nicotinic acetylcholine receptors

Nicotinic acetylcholine receptor of the electric ray Torpedo is the most co mprehensively characterized neurotransmitter receptor. It consists of five subunits (alpha(2)beta gamma delta), amino acid sequences bf which were det ermined by cDNA cloning and, sequencing. The shape and dimensions of the re ceptor were determined by electron cryomicroscopy. it has two agonist/compe titive antagonist binding sites that are Situated between subunits near the membrane surface, The receptor ion channel is formed by five transmembrane helices (M2) of all five subunits, The position of the binding site for no ncompetitive ion channel blockers was localized by photoaffinity labeling:a nd site-directed mutagenesis. The intrinsic feature of the receptor structu re is the position of the agonist/competitive antagonist binding sites in c lose vicinity to the-ion channel spanning the bilayer membrane; This peculi arity may substancially enhance allosteric transitions transforming the lig and binding into the channel opening and physiological response. Muscle nic otinic acetylcholine receptors from birds-and mammals are also pentaoligome rs consisting of four different subunits (alpha(2)beta gamma delta or alpha (2)beta epsilon delta) with high homology to the Torpedo receptor. Apparent ly, pentaoligomeric structure is the main feature of all nicotinic receptor s both muscle and neuronal; however the neuronal ones are formed only by tw o subunit types (alpha and beta) or are even pentahomomers (alpha 7 neurona l receptors). All nicotinic receptors are ligand-gated ion channels, the pr operties of the channels being essentially determined by amino acid residue s forming M2 transmembrane fragments.