alpha-Bungarotoxin receptors contain alpha 7 subunits in two different disulfide-bonded conformations

Neuronal nicotinic alpha 7 subunits assemble into cell-surface complexes th at neither function nor bind alpha-bungarotoxin when expressed in tsA201 ce lls. Functional alpha-bungarotoxin receptors are expressed if the membrane- spanning and cytoplasmic domains of the alpha 7 subunit are replaced by the homologous regions of the serotonin-3 receptor subunit. Bgt-binding surfac e receptors assembled from chimeric alpha 7/serotonin-3 subunits contain su bunits in two different conformations as shown by differences in redox stat e and other features of the subunits. In contrast, alpha 7 subunit complexe s in the same cell line contain subunits in a single conformation. The appe arance of a second alpha 7/serotonin-3 subunit conformation coincides with the formation of alpha-bungarotoxin-binding sites and intrasubunit disulfid e bonding, apparently within the alpha 7 domain of the alpha 7/serotonin-3 chimera. In cell lines of neuronal origin that produce functional alpha 7 r eceptors, alpha 7 subunits undergo a conformational change similar to alpha 7/serotonin-3 subunits. alpha 7 subunits, thus, can fold and assemble by t wo different pathways. Subunits in a single conformation assemble into nonf unctional receptors, or subunits expressed in specialized cells undergo add itional processing to produce functional, alpha-bungarotoxin-binding recept ors with two alpha 7 conformations. Our results suggest that alpha 7 subuni t diversity can be achieved postranslationally and is required for function al homomeric receptors.