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

Biopolymers. 1993 Jul;33(7):1123-34. doi: 10.1002/bip.360330714.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antigen-Antibody Reactions*
  • Autoantigens / chemistry*
  • Autoantigens / immunology
  • Binding Sites
  • Binding Sites, Antibody
  • Computer Simulation*
  • Immunodominant Epitopes / chemistry*
  • Immunodominant Epitopes / immunology
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / immunology
  • Protein Binding
  • Protein Conformation*
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / immunology
  • Thermodynamics
  • Torpedo

Substances

  • Antibodies, Monoclonal
  • Autoantigens
  • Immunodominant Epitopes
  • Peptide Fragments
  • Receptors, Nicotinic