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to con-formational changes and the capability of selective binding of classes of ligands (Conti-Tronconi et al., unpublished).
KeywordsAcetylcholine Receptor Nicotinic Acetylcholine Receptor Nicotinic Cholinergic Receptor Sequence Portion Acetylcholine Recep
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- Chibber BA, Martin BM, Walkinshaw MD, Saenger W, Maelicke A (1983) The sites of neurotoxicity in α-cobratoxin. In: Hucho F, Ovchinnikov YA (eds) Toxins as tools in neurochemistry, Walter de Gruyter & Co., Berlin - New York, pp 141–150Google Scholar
- Conti-Tronconi BM, Fels G, McLande K, Tang F, Bellone M, Kokla A, Tzartos S, Milius R, Maelicke A (1989) Use of synthetic peptides and high affinity protein ligands for structural studies of central and peripheral nicotinic receptors. This volume, pp 291–309Google Scholar
- Gershoni JM, Aronheim A, Mosckovitz R, Ohana B, Rusu I (1989) Towards an understanding and use of the cholinergic binding site. This volume, pp. 345–352Google Scholar
- Gotti C, Longhi R, Frigerio F, Bolognesi M, Fornasari D, Racchetti G, Mazzola G, Clementi F (1989) Structure, con¬formation and immunological analysis of peptide 188–201, the putative binding site for α-bungarotoxin in the α sub-unit of acetylcholine receptor. This volume, pp. 327–343Google Scholar
- Gotti C, Mazzola G, Longhi R, Fornasari D, Clementi F (1987) The binding site for α-bungarotoxin resides in the sequence 188–201 of the α-subunit of acetylcholine receptor: structure, conformation and binding characteristics of peptide (Lys)188–201. Neurosci Lett 82: 113–119PubMedCrossRefGoogle Scholar
- Maelicke A (1988) Structure and function of the nicotinic acetylcholine receptor. In: Born GVR, Farah A, Herken H, Welch AD (eds) Handbook of experimental pharmacology. Volume: “The Cholinergic Synapse” Whittaker VP (ed) Vol 86, Springer-Verlag Berlin-Heidelberg-New York-Tokyo, pp 267–313Google Scholar