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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
Author(s) -
Tsikaris Vassilios,
Detsikas Evangelos,
SakarellosDaitsiotis Maria,
Sakarellos Constantinos,
Vatzaki Efstratia,
Tzartos Socrates J.,
Marraud Michel,
Cung Manh Thong
Publication year - 1993
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360330714
Subject(s) - chemistry , torpedo , monoclonal antibody , peptide , molecular dynamics , acetylcholine receptor , antibody , stereochemistry , sequence (biology) , molecular recognition , conformational change , biophysics , receptor , biochemistry , molecule , computational chemistry , immunology , biology , organic chemistry
Abstract The conformational properties of two [ D ‐A 70 , A 76 ] and [Aib 70 , A 76 ] analogues of the α67–76 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 [A 76 ] 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 A 70 , at a crucial position, by the D ‐A 70 or Aib 70 , 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. © 1993 John Wiley & Sons, Inc.