Specific interaction of central nervous system myelin basic protein with lipids. Specific regions of the protein sequence protected from the proteolytic action of trypsin

The tryptic hydrolysis of the basic protein of central nervous system myelin (A₁ basic protein) and of A₁ basic-lipid complexes was studied. The tryptic digestion was monitored by “finger printing”, column chromatography and amino acid analysis of the resulting pure peptides.Specific regions of the protein sequence were found to be protected from the hydrolytic action of the trypsin only after the protein was recombined with specific lipids. The degree of protection was in the order: cerebroside sulphate > acidic lipid fraction of myelin > phosphatidylsrine = total lipid extract of myelin. The protected Lys-X, Arg-X bonds were all situated in the region amino acid 20 to amino acid 113 of the intact protein. This region contains the (proline)₃ bend in the protein which is stabilized by interaction with lipids and also the encephalitogenic site for monkey and rabbit.From the results reported in this publication we would like to suggest a specific interaction between a region of the A₁ basic protein molecule and cerebroside sulphate. Differences in A₁ basic protein-lipid interaction in different animals arising from differences in lipid composition and fatty acid composition of the different lipid species combined with minor changes in the protein sequence could explain the species variability of the encephalitogenic sites of the A₁ basic protein.