S. Rakhilin et al., alpha-Bungarotoxin receptors contain alpha 7 subunits in two different disulfide-bonded conformations, J CELL BIOL, 146(1), 1999, pp. 203-217
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.