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Direct structural localization of two toxin-recognition sites on an ACh receptor protein

Nature volume 299, pages 81–84 (1982)Cite this article

Abstract

One of the most actively studied chemoreceptors is the acetylcholine receptor (AChR) in the postsynaptic membranes of neuromuscular junctions and electrocytes. The AChR from Torpedo is a membrane protein, each molecule comprising five polypeptide chains1,2: two α-chains of molecular weight (Mr) 40,000, and three homologous chains of Mr 50,000 (β), 60,000 (γ) and 65,000 (δ). Only the α-summits seem to carry the specific recognition sites for agonists and antagonists2. As snake α-neurotoxins seem to bind highly specifically and quasi-irreversibly to these sites we performed a structural analysis to localize the α-subunits, using as marker native α-bungarotoxin (α-BTX, Mr 8,000; ref. 3). We report here the results obtained at 20 Å resolution by electron microscopy and single-particle image averaging4, which reveal two well-defined regions within the AChR structure5,6 where the mass increases significantly on binding of α-BTX. One of these (α1) is adjacent to the region where the δ-subunit has been located6; the second region (α2) is diametrically across the molecule, ∼50 Å away from the δ-subunit and also from (α1). The topography revealed by direct structural analysis can explain the results of previous nearest-neighbour cross-linking studies2,7.

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Author notes

  1. D.-Ch. Neugebauer

    Present address: Zoologisches Institut der Universität Münster, Hüfferstrasse 1, D4400, Münster, FRG

Authors and Affiliations

  1. Max-Planck-Institut für Biophysikalische Chemie (Karl-Friedrich-Bonhoeffer-Institut), D3400, Göttingen, FRG

    H. P. Zingsheim, F. J. Barrantes, W. Hänicke & D.-Ch. Neugebauer

  2. Center for Laboratories and Research, New York State Department of Health, Albany, New York, 12201, USA

    J. Frank

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  4. W. Hänicke
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  5. D.-Ch. Neugebauer
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Zingsheim, H., Barrantes, F., Frank, J. et al. Direct structural localization of two toxin-recognition sites on an ACh receptor protein. Nature 299, 81–84 (1982). https://doi.org/10.1038/299081a0

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