EXTRACELLULAR DOMAINS MEDIATING EPSILON SUBUNIT INTERACTIONS OF MUSCLE ACETYLCHOLINE-RECEPTOR

LIGAND-gated ion channels, a major class of cell-surface proteins, have a pseudosymmetric structure with five highly homologous subunits arranged around a central ion pore 1. The correct assembly of each channel, whose subunit composition varies with cell type and stage of development, requires specific recognition between the subunits 2-4. Assembly of the pentameric form of the acetylcholine receptor from adult muscle (AChR; alpha-2-beta-epsilon-delta) proceeds by a stepwise pathway starting with the formation of the heterodimers, alpha-epsilon and alpha-delta. The heterodimers then associate with the beta-subunit and with each other to form the complete receptor 5-7,21. We have now determined which parts of the subunits mediate the interactions during assembly of the adult form of the receptor from mouse muscle by using a chimaeric subunit in which the N-terminal and C-terminal extracellular domains are derived from the E subunit with the remainder from the beta-subunit. The epsilon and beta-subunits were chosen because the epsilon-subunit forms a heterodimer with the alpha-subunit in the pathway for assembly of the receptor, whereas the beta-subunit does not. The epsilon-beta chimaera can substitute for the epsilon but not the beta-subunit in the oligomeric receptor, indicating that the alpha-subunit specifically recognizes an extracellular domain of the epsilon-subunit.