3-DIMENSIONAL SOLUTION STRUCTURE OF THE COMPLEX OF ALPHA-BUNGAROTOXINWITH A LIBRARY-DERIVED PEPTIDE

The solution structure of the complex between alpha-bungarotoxin (alph a-BTX) and a 13-residue library-derived peptide (MRYYESSLKSYPD) has be en solved using two-dimensional proton-NMR spectroscopy. The bound pep tide adopts an almost-globular conformation resulting from three turns that surround a hydrophobic core formed by Tyr-11 of the peptide. The peptide fills an alpha-BTX pocket made of residues located at fingers I and II, as well as at the C-terminal region. Of the peptide residue s, the largest contact area is formed by Tyr-3 and Tyr-4. These findin gs are in accord with the previous data in which it had been shown tha t substitution of these aromatic residues by aliphatic amino acids lea ds to loss of binding of the modified peptide with alpha-BTX. Glu-5 an d Leu-8, which also remarkably contribute to the contact area with the toxin, are present in all the library-derived peptides that bind stro ngly to alpha-BTX. The structure of the complex may explain the fact t hat the library-derived peptide binds alpha-BTX with a 15-fold higher affinity than that shown by the acetylcholine receptor peptide (alpha 185-196). Although both peptides bind to similar sites on alpha-BTX, t he latter adopts an extended conformation when bound to the toxin [Bas us, V., Song, G. & Hawrot, E. (1993) Biochemistry 32, 12290-12298], wh ereas the library peptide is nearly globular and occupies a larger sur face area of alpha-BTX binding site.