Abstracts

Knowledge of the tertiary structure of myelin basic protein (MBP) is essential to understanding the organi sation of the myelin membrane and the mechanisms of development of autoimmunity in mult iple sclerosis. We have initiated high-resolution electron micro scopical (EM) analyses of MBP to determine its structure. When imaged as individual particles, MBP demonstrates a “C” shap e in proj ect ion, of approximately 1.5 nm in thickness and 8 nm in length . Two-dimensional crystallisation experiments on MBP using mono layers of DHAA (dehydroabietylamine) or lipid mixtures (phosphatidylcholine, phosphatid ylserine, dioleoyl phosphatidylethanolamine, galactocerebroside) yielded lamellar or occasion ally cry stalline structures with a repeating pattern of packed protein molecules with a unit cell size of approximately 2 nm by 7 nm, suggesting that the MBP extends itself upon interac tion with the monolayer. Molecular modelling of MBP based on a proposal by Stoner (J. Neurochem. 43 , 433–447,1984), using coo rdin ates of the B sheet backbone of bacteriochlorophyll A protein and energy min imis ation, yielded a compact structure of size and appearance consistent with both our EM data and with biochemical data on accessibility of specific sires (e.g., Ser7, Thr98) to modification . The bend of the C shape appears due to a natura l curvature in the B sheet. These results are fully congruous with MBP having a regular secondary structure and domains that are potentially flexible with respect to one another. This work was supported by the Multiple Sclerosis Society of Canada.