Structure and molecular arrangement of proteolipid protein of central nervous system myelin.

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Abstract
Proteolipid protein (PLP) on CNS myelin is one of the most hydrophobic integral membrane proteins. It consists of a 276-residue-long polypeptide chain with 5 strongly hydrophobic sequences of 26, 30, 39, 12 and 36 residues, respectively, linked by highly charged hydrophilic sequences. Hyposmotically dissociated bovine myelin cleaved into smaller fragments, whereas basic myelin protein remained essentially unaltered. The proteins and tryptic peptides of myelin were separated after the removal of the short, water-soluble peptides into 3 large fragments of 11, 7.3 and 9.0 kDa [kilodalton], respectively. They were characterized by their molecular mass and NH2-terminal amino acid sequences, which proved that trypsin cleaved predominantly at Arg-97 yielding the 11-kDa fragment from Gly-1 through Arg-97, at Arg-126 releasing the 7.3-kDa fragment from Gly-127 through Lys-191, and at Lys-191 releasing the 9-kDa fragment from Thr-192 through Phe-276. PLP may be integrated into the lipid bilayer of myelin with the NH2 terminus and 3 positively charged hydrophilic loops oriented toward the extracytosolic side of the lipid bilayer. Basic myelin protein remains protected against tryptic cleavage, which indicates its apposition to the cytosolic side of the membrane. These cleavage sites of trypsin support the suggested orientation of PLP in the myelin membrane and thereby extend knowledge about the molecular arrangement of the components of this membrane. In demyelinating processes membrane desintegration could be initiated by proteolysis at the external surfaces of proteolipid protein in a similar way as described here.