Determinants Responsible for Assembly of the Nicotinic Acetylcholine Receptor

The assembly of the four homologous, but distinct, α, β, γ, and δ subunits of the nicotinic acetylcholine receptor (nAChR) into the pentamer α₂βγδ presents a unique opportunity to delineate the individual amino acid side chains that contribute to the assembly process, and to examine the pathway responsible for subunit assembly and expression at the cell surface. It is well established that subunits assemble into the circular order of αγαδβ, where the γ subunit resides between the two α subunits and two binding sites are found at the αγ and αδ interfaces (for detailed reviews, see Karlin and Akabas, 1995; Hucho et al., 1996). Chirality of the order of the subunits has also been proposed on the basis of cross-linking of toxins with known structures to the receptor (Machold et al., 1995; Utkin et al., 1997). The subunits are glycoproteins composed of...