Evidence for Multipoint Attachment of Ligands to the Nicotinic Acetylcholine Receptor
Binding of 125I-labelled α-bungarotoxin (αBTX) and of several 3H-labelled αBTX-competitive anti-nAChR antibodies suggest that the cholinergic binding site(s) are “discontinuous”, i.e. they are formed by several sequence segments which are well separated along the primary structure of the nAChR α-subunit (Conti-Tronconi et al., 1989). Presumably, these non-continuous segments are brought together, by the tertiary folding of the α-subunit, to form the area of the nAChR surface recognized by the neurotoxin and the antibodies. Our data agree with previous reports (Neumann et al., 1986; Gotti et al., 1987; Ralston et al., 1987; Gershoni 1987; Gotti et al., 1989; Gershoni et al., 1989) in that the region around cysteines 192 and 193 forms a major component of the toxin binding site. They result in a different model of the cholinergic binding site, however, in that they suggest a rather intricately structured binding region, with particular sensitivity to con-formational changes and the capability of selective binding of classes of ligands (Conti-Tronconi et al., unpublished).
KeywordsTyrosine Cysteine Dimethyl Disulfide Acetylcholine
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