title: Racemization of individual aspartate residues in human myelin basic protein.
abstract: Human myelin basic protein (MBP), a long-lived brain protein, undergoes gradual racemization of its amino acids, primarily aspartic acid and serine. Purified protein was treated at neutral pH with trypsin to yield peptides that were separated by HPLC using a C18 column. Twenty-nine peptides were isolated and analyzed for amino acid composition and aspartate racemization. Each aspartate and asparagine in the protein was racemized to a different extent, ranging from 2.2 to 17.1% D isomer. When the racemization was examined in terms of the beta-structure model of MBP, a correlation was observed in which six aspartate/asparagine residues assumed to be associated with myelin membrane lipids showed little racemization (2.2-4.9% D isomer), whereas five other aspartate residues were more highly racemized (9.9-17.1% D isomer). Although the observed aspartate racemization may be related to steric hindrance by neighboring residues and/or the protein secondary structure, interaction of aspartates with membrane lipids may also be a major factor. The data are compatible with a model in which each MBP molecule interacts with adjacent cytoplasmic layers of myelin membrane through a beta-sheet on one surface and loops and helices on the other surface, thereby stabilizing the myelin multilamellar structure.
mesh_terms: D000368:Aged; D000591:Amino Acid Isomerases / Q000378:metabolism*; D001216:Asparagine / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism*; D010434:Pepsin A / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011487:Protein Conformation; D014357:Trypsin / Q000378:metabolism
chemical_list: D004676:Myelin Basic Protein; D010446:Peptide Fragments; D001224:Aspartic Acid; D001216:Asparagine; D014357:Trypsin; D010434:Pepsin A; D000591:Amino Acid Isomerases; C019749:aspartate racemase