title: Conformational studies of immunodominant myelin basic protein 1-11 analogues using NMR and molecular modeling.
abstract: Τwo dimensional nuclear magnetic resonance studies complimented by molecular dynamics simulations were conducted to investigate the conformation of the immunodominant epitope of acetylated myelin basic protein residues 1-11 (Ac-MBP(1-11)) and its altered peptide ligands, mutated at position 4 to an alanine (Ac-MBP(1-11)[4A]) or a tyrosine residue (Ac-MBP(1-11)[4Y]). Conformational analysis of the three analogues indicated that they adopt an extended conformation in DMSO solution as no long distance NOE connectivities were observed and seem to have a similar conformation when bound to the active site of the major histocompatibility complex (MHC II). The interaction of each peptide with MHC class II I-A(u) was further investigated in order to explore the molecular mechanism of experimental autoimmune encephalomyelitis induction/inhibition in mice. The present findings indicate that the Gln(3) residue, which serves as a T-cell receptor (TCR) contact site in the TCR/peptide/I-A(u) complex, has a different orientation in the mutated analogues especially in the Ac-MBP(1-11)[4A] peptide. In particular the side chain of Gln(3) is not solvent exposed as for the native Ac-MBP(1-11) and it is not available for interaction with the TCR.
authors: Department of Chemistry, University of Patras, 26500, Patras, Greece.
authors: Despina
authors: D
authors: Laimou
authors: Eliada
authors: E
authors: Lazoura
authors: Anastassios N
authors: AN
authors: Troganis
authors: Minos-Timotheos
authors: MT
authors: Matsoukas
authors: Spyros N
authors: SN
authors: Deraos
authors: Maria
authors: M
authors: Katsara
authors: John
authors: J
authors: Matsoukas
authors: Vasso
authors: V
authors: Apostolopoulos
authors: Theodore V
authors: TV
authors: Tselios
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D005802:Genes, MHC Class II; D051379:Mice; D056004:Molecular Dynamics Simulation; D009154:Mutation; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C405722:myelin basic protein 1-11