Further investigation of human myelin basic protein (HBP) extracted from whole CNS tissue or from CNS myelin, has confirmed the existence of two and possibly three HBP-related polypeptides, approximately 1.5 K smaller than the 18.5 K major HBP. These polypeptides differ in charge from the major 18.5 K HBP, component 1, by two negative charges. This difference is caused by the deletion of either the first 17 N-terminal residues, or 19 residues from the C-terminal part of the molecule. Tryptic digestion of the thrombic peptides of HBP (fraction 3), which is a 50/50 mix of 18.5 and 17.0 K polypeptides, gave indication that one of the 17 K polypeptides had a deletion immediately N-Terminal to the tryptophan. We have developed a new procedure on the FPLC (fast protein liquid chromatography) system to separate the 17 K polypeptides from the 18.5 K HBP, component 3. In collaboration with Dr. Henry Krutzsch, NCI, we have shown that both the 17 K and the 18.5 K have blocked N-terminals and the same C terminus. Our current tryptic peptide mapping by HPLC allows us to identify all of the tryptic peptides of HBP. Therefore, we can eventually identify all the deletions in the 17 K protein, which probably arise from m-RNA processing rather than autolysis in situ. We are also investigating the relation of phosphorylation to the conformation of bovine myelin basic protein, in collaboration with Dr. Audrey Stone. Circular dichroic studies show that the percent of ordered structure (Beta-turns plus Beta structure) increases up to 46% with increased phosphate on the BP molecule. This indicates that BP has a significant tendency to form ordered structures in aqueous solution and suggests that BP phosphorylation may play a role in the way basic protein fits into the myelin in situ.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Intramural Research (Z01)
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U.S. National Institute of Mental Health
United States
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