NMR structural elucidation of myelin basic protein epitope 83-99 implicated in multiple sclerosis

作者：Spyranti Zinovia; Tselios Theodore; Deraos George; Matsoukas John; Spyroulias Georgios A^*

来源：Amino Acids, 2010, 38(3): 929-936.

DOI：10.1007/s00726-009-0301-4

• MBP
• Multiple sclerosis
• NMR conformational analysis

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.

• 出版日期2010-3