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.
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.
Tsikaris
V
V
Department of Chemistry, University of Ioannina, Greece.
Detsikas
E
E
Sakarellos-Daitsiotis
M
M
Sakarellos
C
C
Vatzaki
E
E
Tzartos
S J
SJ
Marraud
M
M
Cung
M T
MT
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
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D011978:Receptors, Nicotinic