title: NMR structural elucidation of myelin basic protein epitope 83-99 implicated in multiple sclerosis.
abstract: Myelin basic protein peptide 83-99 (MBP83-99) is the most immunodominant epitope playing a significant role in the multiple sclerosis (MS), an autoimmune disease of the central nervous system. Many peptide analogues, linear or cyclic have been designed and synthesized based on this segment in order to inhibit the experimental autoimmune encephalomyelitis, the best well-known animal model of MS. In this study, the solution structural motif of MBP(83-99) has been performed using 2D (1)H-NMR spectroscopy in dimethyl sulfoxide. A rather extended conformation, along with the formation of a well defined alpha-helix spanning residues Val(87)-Phe(90) is proposed, as no long-range NOE are presented. Moreover, the residues of MBP peptide that are important for T-cell receptor recognition are solvent exposed. The spatial arrangement of the side chain all over the sequence of our NMR based model exhibits great similarity with the solid state model, while both TCR contacts occupy the same region in space.
authors.affiliation: Department of Pharmacy, University of Patras, 265 04 Panepistimioupoli, Rion, Greece.
authors.forename: Zinovia
authors.initials: Z
authors.lastname: Spyranti
authors.forename: Theodore
authors.initials: T
authors.lastname: Tselios
authors.forename: George
authors.initials: G
authors.lastname: Deraos
authors.forename: John
authors.initials: J
authors.lastname: Matsoukas
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Spyroulias
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000276:immunology*; D008958:Models, Molecular; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology*; D011487:Protein Conformation; D012984:Software; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: D016056:Immunodominant Epitopes; C499048:MBP protein, human; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D012997:Solvents; D014157:Transcription Factors; C104448:myelin basic protein 83-99; D004121:Dimethyl Sulfoxide