title: Structural basis of antibody cross-reactivity: solution conformation of an immunogenic peptide fragment containing both T and B epitopes.
abstract: A synthetic octadecapeptide with the amino acid sequence of residues 23-40 of toxin alpha from Naja nigricollis, cyclized with a disulfide bridge between residues 23 and 40, induces antibodies that cross-react with toxin alpha. We report a structural analysis of this peptide in aqueous solution using NMR spectroscopy and molecular modeling. Structures compatible with the 151 obtained NMR distance restraints were generated using a random simulated annealing protocol followed by restrained high-temperature dynamics and energy minimization. The generated structures are compared with that of the corresponding sequence in the native 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 region 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 structures in the peptide. Residues 30-33 form a reverse turn in both the peptide and the toxin. Residues Val-27, Trp-28, Ile-35, and Ile-36 form a hydrophobic cluster. The similar, reverse-turn fold of residues 30-33 in the peptide and the toxin may be associated with the immunogenic cross-reactivity.
authors.affiliation: CEA, Département d'Ingénierie et d'Etudes des Protéines, Gif-sur-Yvette, France.
authors.forename: P
authors.initials: P
authors.lastname: Cuniasse
authors.forename: A
authors.initials: A
authors.lastname: Thomas
authors.forename: J C
authors.initials: JC
authors.lastname: Smith
authors.forename: H L
authors.initials: HL
authors.lastname: Thanh
authors.forename: M
authors.initials: M
authors.lastname: Léonetti
authors.forename: A
authors.initials: A
authors.lastname: Ménez
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003039:Cobra Neurotoxin Proteins / Q000737:chemistry* / Q000276:immunology; D003429:Cross Reactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000906:Antibodies; D003039:Cobra Neurotoxin Proteins; D010446:Peptide Fragments; C025154:alpha-cobratoxin