Cross-linking of lipid bilayers by central nervous system myelin basic protein: aggregation of free and vesicle-bound protein.

Abstract

Central nervous system myelin basic protein binds to the zwitterionic lipid, egg diacylphosphatidylcholine, over a wide range of pH and ionic strength. Lipid vesicles containing the protein have been observed to increase in size and to aggregate. The size increase is most marked at very low ionic strengths whereas aggregation is evident at ionic strengths from 0.001 to 0.35. The pH and ionic-strength dependence of this aggregation closely follows that of the self-association of the protein, suggesting that vesicle association is mediated by binding between polypeptides attached to different vesicles. Basic protein is monomeric at low pH but above pH 6 self-associates yielding primarily small oligomers (probably dimers) and minor amounts of higher species. It is envisaged that each protein molecule possesses two distinct binding sites, one capable of association with lipid bilayers and the second with another protein molecule. Basic protein is found predominantly on the intracellular surface of the myelin membrane. Given the ability of the protein to act as a bridge between lipid bilayer vesicles in vitro it is proposed that it may perform a similar function in vivo, serving to cross-link the inner surfaces of the oligodendroglial cell membrane. This protein function could lead to formation of the long cellular processes which encircle the nerve cell axon and could assist in stabilizing the highly ordered myelin structure which results.