NMR studies of myelin basic protein. X. Conformation of a determinant encephalitogenic in the rabbit.

Residues 67 to 75 in myelin basic protein from several species comprise the sequence Thr-His-Tyr-Gly-Ser-Leu-Pro-Gln-Lys that acts as an encephalitogenic determinant in the rabbit. Proton magnetic resonance spectra of human, bovine and porcine proteins display nuclear Overhauser effects between the delta-CH of Tyr-69 and the delta-CH3 of Leu-72, which indicate reverse-turn conformations about the Gly-Ser residues. This effect occurs also in physiological saline solution at pH 6.0 but in dimethylsulfoxide solution the nuclear Overhauser effect disappears. Circular dichroism indicates that the protein when bound to ganglioside micelles acquires 30-40% alpha-helical conformation, but the reverse turn still persists in the sequence of the rabbit encephalitogen. These results suggest that the encephalitogenic region of the protein remains at the aqueous interface of the micelles.