alpha -Bungarotoxin Receptors Contain alpha 7 Subunits in Two Different Disulfide-bonded Conformations

Neuronal nicotinic alpha 7 subunits assemble into cell-surface complexes that neither function nor bind alpha -bungarotoxin when expressed in tsA201 cells. 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 surface receptors assembled from chimeric alpha 7/serotonin-3 subunits contain subunits in two different conformations as shown by differences in redox state and other features of the subunits. In contrast, alpha 7 subunit complexes in the same cell line contain subunits in a single conformation. The appearance of a second alpha 7/serotonin-3 subunit conformation coincides with the formation of alpha -bungarotoxin-binding sites and intrasubunit disulfide 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 receptors, alpha 7 subunits undergo a conformational change similar to alpha 7/serotonin-3 subunits, alpha 7 subunits, thus, can fold and assemble by two different pathways. Subunits in a single conformation assemble into nonfunctional receptors, or subunits expressed in specialized cells undergo additional processing to produce functional, alpha -bungarotoxin-binding receptors with two alpha 7 conformations. Our results suggest that alpha 7 subunit diversity can be achieved postranslationally and is required for functional homomeric receptors.