Compared structures of the free nicotinic acetylcholine receptor main immunogenic region (MIR) decapeptide and the antibody-bound [A76] MIR analogue: A molecular dynamics simulation from two-dimensional NMR data

Autor: Constantinos Sakarellos, Maria Sakarellos-Daitsiotis, Michel Marraud, Vassilios Tsikaris, Socrates J. Tzartos, Piotr Orlewski, Efstratia H. Vatzaki, Manh-Thong Cung
Rok vydání: 1996
Předmět:
alpha-subunit
Models
Molecular
Protein Folding
Magnetic Resonance Spectroscopy
Molecular model
Protein Conformation
Peptide
Antigen-Antibody Complex
Receptors
Nicotinic
Torpedo
Biochemistry
Protein Structure
Secondary
law.invention
residues
Epitopes
Protein structure
law
dmso solvent box
chemistry.chemical_classification
Chemistry
torpedo
magnetic-resonance
Antibodies
Monoclonal
General Medicine
Nuclear magnetic resonance spectroscopy
Antigen-antibody interaction
two-dimensional nmr
dimethyl-sulfoxide
synthetic peptides
Protein folding
Stereochemistry
monoclonal-antibodies
Biophysics
alpha-67-76 fragment
Biomaterials
antigen
Animals
Computer Simulation
Dimethyl Sulfoxide
Acetylcholine receptor
myasthenia gravis
acetylcholine receptor
Organic Chemistry
crystal-structure
Hydrogen Bonding
molecular dynamics
Peptide Fragments
antigenic peptide
antigen-antibody interaction
Zdroj: Biopolymers. 40:419-432
ISSN: 1097-0282
0006-3525
DOI: 10.1002/(sici)1097-0282(1996)40:5<419::aid-bip1>3.0.co;2-z
Popis: Monoclonal antibodies against the main immunogenic region (MIR) of the muscle acetylcholine receptor (AChR) are capable of inducing experimental myasthenia gravis (MG) in animals. The epitope of these antibodies has been localized between residues 67 and 76 of the AChR cu-subunit. The conformation in solution of the Torpedo californica MIR peptide and of its [A(76)] MIR analogue have been analyzed using molecular modeling based on nmr interproton distances and J-derived phi dihedral angles. Molecular dynamics simulations including dimethyl-sulfoxide as explicit solvent have been carried out on the free MIR peptide. Calculation of the structure of the [A(76)]MIR analogue bound to an anti-MIR monoclonal antibody have been performed in the presence of water molecules. A tightly folded structure appears for bothpeptides with a beta-folded N-terminal N-68-P-A-D-71 sequence of type I in the free state and type III in the mAb6-bound state. The C-terminal sequence is folded in two different ways according to the result in the free and bound state of the peptides: two overlapping beta/beta ar beta/alpha turns result in a short helical sequence in the free MIR peptide, whereas the bound analogue is folded by an uncommon hydrogen bond closing an 11-membered, cycle. This structural evolution is essentially the result of the reorientation of the hydrophobic side chains that are probably directly involved in peptide-antibody recognition. (C) 1997 John Wiley & Sons, Inc. Biopolymers
Databáze: OpenAIRE
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