title: Structural and functional aspects of the nicotinic acetylcholine receptor.
abstract: The molecular structure of nicotinic acetylcholine receptors (AcChR) from different peripheral tissues and from different brain areas has been studied. AcChRs from Torpedo and Electrophorus electric organ and from piscine, avian, and mammalian muscle have been shown to be highly conserved proteins composed of four types of homologous subunits (alpha, beta, gamma, and delta) which associate in a stoichiometry alpha 2 beta 1 gamma 1 delta 1 to form a pseudosymmetric pentameric complex molecule. Genealogical analysis suggests that all the subunits of these AcChR derive from a common ancestral gene and that the divergence occurred very early in the evolution of the receptor. This shared ancestry and the very early divergence of the four subunits, as well as their highly conserved structures along the animal evolution, suggests that each of the subunits evolved to perform specific crucial roles in the function of the AcChR complex. In Torpedo the two alpha-subunits present in the AcChR molecule are glycosylated to a different extent. This may be the reason why the binding sites for cholinergic ligands that are located on the alpha-subunits are non-equivalent. The pseudosymmetric pentameric complex has all the properties of a physiological receptor with respect to known parameters leading to postsynaptic depolarization, and therefore contains the molecular structure/structures that constitute a cation selective channel for transport across the membrane. The complex also contains recognition sites for acetylcholine, cholinergic antagonists, polypeptide neurotoxins, small molecule neurotoxins, and local anesthetics. Therefore a multiplicity of receptor-ligand associations are possible. This leads to more complex models of such interactions than previously considered.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001717:Birds; D001921:Brain / Q000378:metabolism; D002417:Cattle; D004593:Electrophorus; D005399:Fishes; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013045:Species Specificity; D014101:Torpedo
chemical_list: D008024:Ligands; D011950:Receptors, Cholinergic