Evidence for Multipoint Attachment of Ligands to the Nicotinic Acetylcholine Receptor

  • Alfred Maelicke
  • Gregor Fels
  • Bianca M. Conti-Tronconi
Conference paper
Part of the NATO ASI Series book series (volume 32)


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to con-formational changes and the capability of selective binding of classes of ligands (Conti-Tronconi et al., unpublished).


Acetylcholine Receptor Nicotinic Acetylcholine Receptor Nicotinic Cholinergic Receptor Sequence Portion Acetylcholine Recep 
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  1. Amit AG, Mariuzza RA, Phillips SEV, Poljak RJ (1986) Three- dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science (Washington DC) 232: 747–753CrossRefGoogle Scholar
  2. 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
  3. 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
  4. Conti-Tronconi, B.M. & Raftery, M.A. (1982) The nicotinic cholinergic receptor: correlation of molecular structure with functional properties. Annu. Rev. Biochem. 51, 491–530PubMedCrossRefGoogle Scholar
  5. Fels G, Wolff EK, Maelicke A (1982) Equilibrium binding of acetylcholine to the membrane-bound acetylcholine receptor. Eur J Biochem 127: 31–38PubMedCrossRefGoogle Scholar
  6. Gershoni JM (1987) Expression of the a-bungarotoxin binding site of the nicotinic acetylcholine receptor by Escherichia coli transformants. Proc Natl Acad Sci USA 84: 4318–4321PubMedCrossRefGoogle Scholar
  7. 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
  8. 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
  9. 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
  10. Kang S, Maelicke A (1980) Fluorescein isothiocyanate-labeled α-cobratoxin: biochemical charakterization and interaction with acetylcholine receptor from Electrophorus electricus. J Biol Chem 255: 7326–7332PubMedGoogle Scholar
  11. Maelicke A (1984) Biochemical aspects of cholinergic excitation. Angew Chem Int Ed 23: 195–221CrossRefGoogle Scholar
  12. 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
  13. Maelicke A, Fulpius BW, Klett RP, Reich E (1977) Acetylcholine receptor: responses to drug binding. J Biol Chem 252: 4811–4830PubMedGoogle Scholar
  14. Martin BM, Chibber BA, Maelicke A (1983) The Sites of Neurotoxicity in α-Cobratoxin. J Biol Chem 258: 8714–8722PubMedGoogle Scholar
  15. Neumann D, Barchan D, Safran A, Gershoni JM, Fuchs S (1986) Mapping of the alpha-bungarotoxin binding site within the alpha-subunit of the acetylcholine receptor. Proc Natl Acad Sci USA 83: 3008–3011PubMedCrossRefGoogle Scholar
  16. Ralston S, Sarin V, Thanh HL, Rivier J, Fox JL, Lindstrom J (1987) Synthetic peptides used to locate the α-bungaro-toxin binding site and immunogenic regions on a subunits of the nicotinic acetylcholine receptor. Biochemistry 26: 3261–3266PubMedCrossRefGoogle Scholar
  17. Ruchel R, Watters D, Maelicke A (1981) Molecular forms and hydrodynamic properties of acetylcholine receptor from electric tissue. Eur J Biochem 119: 215–223PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Alfred Maelicke
    • 1
  • Gregor Fels
    • 1
  • Bianca M. Conti-Tronconi
    • 2
  1. 1.Max-Planck-Institut für ErnährungsphysiologieDortmund 1Germany
  2. 2.Department of BiochemistryUniversity of MinnesotaSt. PaulUSA

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