Myelin basic protein.

The fact that central nerve tissue is encephalitogenic has been known since the observation of a post-injection reaction of some rabies victims to the Pasteur vaccine that contained nerve tissue (Brostoff, 1977). Subsequently the encephalitogenic agent in central nerve tissue was traced to a component of the myelin sheath, and a protein was finally isolated that in the presence of complete Freund's adjuvant, was a potent encephalitogen in certain animal species. The encephalitogenicity of the myelin basic protein and the study of experimental allergic encephalomyelitis as a model for multiple sclerosis has meant that structural, functional and immunological features of the protein have been studied in some depth (Carnegie & Dunkley, 1975; Braun & Brostoff, 1977; Rumsby & Crang, 1977). Myelin basic protein in the central nervous system is detected in myelin from both brain and spinal-cord tissue. In myelin from the peripheral nervous system a P, protein resembles the myelin basic protein of the central nervous system in almost all respects (Braun & Brostoff, 1977). Myelin basic protein is not a major component of central nerve tissue until myelination commences (e.g. Adams & Osborne, 1973). Polyacrylamide-gel electrophoresis of myelin (e.g. Waehneldt & Mandel, 1972) and immunocytochemical methods (Sternberger et al., 1978; Hartman et al., 1979) with nerve tissue have been applied to define the location of myelin basic protein in the myelin sheath. More recently, immunocytochemical methods have been applied with particularly good effect to detect myelin basic protein in the cytoplasm of oligodendrocyte cell bodies and their processes and to show that the protein is present in the oligodendrocyte compartment before the onset of myelination (Sternberger et al., 1978; Hartman et al., 1979). This specific localization of myelin basic protein on the oligodendrocyte-myelin-sheath compartment has revealed that some processes from oligodendrocytes are over 30pm long (Sternberger et al., 1978). Myelin in the central nervous system contains two major protein components, the proteolipid protein and the myelin basic protein, which together account for about 80-85% of the total protein of the membrane system (Rumsby & Crang, 1977; Boggs & Moscarello, 1978a; Rumsby, 1978). Of these two main protein species myelin basic protein accounts for about 30% of the total protein of myelin. The ratio of myelin basic protein to proteolipid protein varies depending on the region of the central nervous system (Carnegie & Dunkley, 1975). Central nerve tissue is rich in myelin basic protein because myelin represents a major part of the white matter. There is some 9 g of myelin basic protein in a human brain. The protein can be easily recovered from central nervous tissue and purified by chromatographic procedures (Deibler et al., 1972; Banik & Davison, 1973). However, myelin basic protein is rather unstable and is readily degraded into polypeptide fragments of lower molecular weight during isolation, during purification and on storage. Several methods of assay give molecular weights for myelin basic protein in bovine and human central nerve tissue of 18 300 and 18500 respectively (Carnegie & Dunkley, 1975). The bovine protein contains 169 amino acid residues, and its extremely basic nature is due to the presence of 18 arginine, 13 lysine and 10 histidine residues. The isoelectric point of the protein is above pH 10.6. The complete amino acid sequence of myelin basic protein from bovine, rat and human species has been elucidated (Carnegie, 1971; Brostoff et al., 1974; Dunkley & Carnegie, 1974). Points of interest are a proline-rich sequence at residues 96-101, an absence of thiol groups and the fact that the basic amino acid residues are spaced throughout the polypeptide chain, leaving some short sections of amino acids that lack charged residues and that may be more hydrophobic in character. The N-terminus is acetylated, and arginine107 may occur in free, monomethylated or dimethylated forms (Braun & Brostoff, 1977). Additionally, the protein can be isolated in a phosphorylated condition. Protein kinases in myelin and nerve tissue can phosphorylate specific serine and threonine sites in the myelin basic protein molecule (Braun & Brostoff, 1977; Carnegie et al., 1974). Such sites can be dephosphorylated by the action of phosphoprotein phosphatases (Carnegie & Dunkley, 1975). In myelin basic protein isolated from guinea-pig brain tissue some 50% of the purified protein is unphosphorylated (Deibler et al., 1975); the remaining protein molecules are in various states of modification. Generally, not more than 2mol of phosphate/mol of protein has been detected. The effect of this micro-heterogeneity in myelin basic protein structure on the biological role of the protein is not at all clear. Phosphorylation will alter the net charge on the protein molecule, but will not fully counteract the overall strongly basic nature of the protein. Methylation of the arginine at residue 107 may be important in determining the conformation of the polypeptide around this region of the molecule (Braun & Brostoff, 1977).