STRUCTURAL BASIS OF ANTIBODY CROSS-REACTIVITY - SOLUTION CONFORMATIONOF AN IMMUNOGENIC PEPTIDE FRAGMENT CONTAINING BOTH T-EPITOPE AND B-EPITOPE

A synthetic octadecapeptide with the amino acid sequence of residues 2 3-40 of toxin alpha from Naja nigricollis, cyclized with a disulfide b ridge between residues 23 and 40, induces antibodies that cross-react with toxin alpha. We report a structural analysis of this peptide in a queous solution using NMR spectroscopy and molecular modeling. Structu res compatible with the 151 obtained NMR distance restraints were gene rated using a random simulated annealing protocol followed by restrain ed high-temperature dynamics and energy minimization. The generated st ructures are compared with that of the corresponding sequence in the n ative toxin. The two stretches 23-28 and 37-40 adopt a canonical beta- strand structure in the toxin but are disordered in the peptide. The r egion 28-36 is ordered in both the peptide and the toxin. Residues 28- 30 and 34-36 adopt beta strand structures in the toxin but loop struct ures in the peptide. Residues 30-33 form a reverse turn in both the pe ptide and the toxin. Residues Val-27, Trp-28, Ile-35, and Ile-36 form a hydrophobic cluster. The similar, reverse-turn fold of residues 30-3 3 in the peptide and the toxin may be associated with the immunogenic cross-reactivity.