Nicotinic acetylcholine receptor: Structure, function and main immunogenic region

Abstract

The nicotinic acetylcholine receptor (AChR) family is a member of the ligand-gated ion-channel gene superfamily, which includes the y-aminobutyric acid (GABA) and glycine receptors (Barnard et al., 1987; Stroud et al., 1990). It contains receptors from the post-synaptic membranes of vertebrate neuromuscular junctions, from the electric organs of electric fish (Torpedo and Electrophorus) and from the central nervous systems of vertebrates and insects. These receptors have several structural and functional features in common, but also have many differences (Lucas and Bencherif, 1992). The muscle-type AChR (i.e. that of the neuromuscular junction and fish electric organs) is the best-known member of the AChR family. It is an integral pentameric membrane protein (Popot and Changeux, 1984) formed from four types of subunits in the stoichiometry @yS or OL$ES (Reynolds and Karlin, 1978; Numa, 1987). Three major factors have facilitated its extensive characterisation: (a) the large quantities that can be isolated from the electric organs of fish, (b) the presence of several snake venom neurotoxins, that bind specifically to the AChR and (c) the application of recombinant DNA techniques. In the present review, we will discuss only this type of AChR. Structural and functional studies of the muscle AChR are of great importance as the molecule acts as the autoantigen in the autoimmune disease myasthenia gravis (MG) and in its experimental animal model (Oosterhuis, 1984; Lindstrom et al., 1988; Penn et al., 1992). MG is characterized by weakness and fatiguability of the skeletal muscles. The disease occurs in about 1 in 20,000 people. As the autoantigen is a well characterized molecule, MG represents an excellent model for the study of the molecular interactions involved in a human autoimmune disease.