Recognition of the acetylcholine receptor binding site of a long-chain neurotoxin by toxin-specific monoclonal antibodies

• Published in: Journal of molecular recognition Vol. 3; no. 2; p. 74
• Main Authors: Charpentier, I, Pillet, L, Karlsson, E, Couderc, J, Ménez, A
• Format: Journal Article
• Language: English
• Published: England 01-04-1990
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Binding Sites; Binding, Competitive; Cobra Neurotoxin Proteins - immunology; Cobra Neurotoxin Proteins - metabolism; Elapid Venoms - metabolism; Epitopes; In Vitro Techniques; Molecular Sequence Data; Molecular Structure; Protein Conformation; Receptors, Nicotinic - metabolism
• ISSN: 0952-3499
• DOI: 10.1002/jmr.300030204

The present paper reports the preparation and characterization of two neutralizing monoclonal antibodies (Mabs), called MST1 and MST2, which bind at the central loop of a long-chain neurotoxin from cobra venom. The central loop is a critical region for the binding of the toxin to the nicotinic acetylcholine receptor. Some of the residues incorporated in the epitopes recognized by MST1 and MST2 have been identified on the basis of competition experiments using a set of 'chemical mutants' of the toxin. We show that MST1 and MST2 bind at the base and at the tip of the central loop of the toxin, respectively, however, only MST2 actually overlaps the acetylcholine receptor binding site. Accordingly, only MST2 is capable of recognizing all homologous toxins so far examined. MST2, therefore, mimicks, at least partially, the site by which the nicotinic acetylcholine receptor recognizes a long-chain neurotoxin.