Isolation of several of the charge isomers from both normal and multiple sclerosis (MS) myelin basic protein (MBP) was achieved on CM-52 columns at pH 10.6. In liquid x-ray diffraction and aggregation experiments, corresponding charge isomers were equally effective in the formation of multilayers, demonstrating the dominant role of overall net positive charge. These studies demonstrated that the change in overall charge of MBP of one net positive charge was sufficient to produce large changes in aggregation and in multilayer formation. The x-ray diffraction experiments showed that component 1 was twice as effective as component 2 although they differed in charge by a single positive charge. Component 3 was less effective than component 2 and component "8" was not effective at all. Vesicle aggregation also showed a dependence on net positive charge. In order of decreasing effectiveness, component
Since overall charge on MBP is determined by contributions from the various charge isomers, the relative proportions of these charge isomers favoring the less cationic components could explain the observation that MBP from MS victims was less effective than MBP from normal brain in vesicle aggregation and niultilayer formation. The isolation of rnyelin-containing white matter fractions from both normal and MS tissue in which the loss of some of the mo5t cationic charge isomers was correlated with presence of less compact myelin supports this hypothesis.