title: Conformational requirements for molecular recognition of acetylcholine receptor main immunogenic region (MIR) analogues by monoclonal anti-MIR antibody: a two-dimensional nuclear magnetic resonance and molecular dynamics approach.
abstract: The conformational properties of two [D-A70, A76] and [Aib70, A76] analogues of the alpha 67-76 Torpedo acetylcholine receptor fragment, with low binding capacity for the anti main immunogenic region (MIR) antibodies, were studied in DMSO by two-dimensional nmr techniques and molecular dynamics simulations. The results were compared to the free and bound conformations of the [A76] analogue, which has twice more affinity for the anti-MIR monoclonal antibody 6 (mAb6), than the natural Torpedo sequence. It appeared that a single substitution of the A70, at a crucial position, by the D-A70 or Aib70, could modify completely the conformational behavior of the peptide and reduced its recognition by the anti-MIR antibody. The WNPADY rigid structure at the N-terminal part was essential for antibody recognition. The adjacent more flexible C-terminal sequence (GGIK) gives additional stability to the monoclonal antibody-peptide complex probably due to an adequate orientation of the peptide side chains in the complex, by setting them in close contact with the antibody.
authors.affiliation: Department of Chemistry, University of Ioannina, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Tsikaris
authors.forename: E
authors.initials: E
authors.lastname: Detsikas
authors.forename: M
authors.initials: M
authors.lastname: Sakarellos-Daitsiotis
authors.forename: C
authors.initials: C
authors.lastname: Sakarellos
authors.forename: E
authors.initials: E
authors.lastname: Vatzaki
authors.forename: S J
authors.initials: SJ
authors.lastname: Tzartos
authors.forename: M
authors.initials: M
authors.lastname: Marraud
authors.forename: M T
authors.initials: MT
authors.lastname: Cung
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D001324:Autoantigens / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D001666:Binding Sites, Antibody; D003198:Computer Simulation; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000276:immunology; D013816:Thermodynamics; D014101:Torpedo
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011978:Receptors, Nicotinic