Conformation of myelin basic protein and its role in myelin formation.
High resolution 13C and 1H NMR spectra of myelin basic protein over a range of pH and concentrations indicate that intramolecular folding of the polypeptide chain occurs in aqueous solution in the region of residues 85 to 116. At pH 4 in D2O solution, the 13C resonances due to nonprotonated carbons of phenylalanine and tryptophan are broadened and chemically shifted compared to the same resonances when the protein is dissolved in 6M guanidinium hydrochloride. These residues occur in the region of the polypeptide chain in which the intramolecular folding may occur. As the pH is raised and the positive charge on the protein reduced from 28 to 18, intermolecular aggregation occurs, which appears to involve these same folded regions. Data on T1 (longitudinal relaxation times) of protons indicate also that amino-acid sidechains vary considerably in their motional freedoms. The concentration dependence of the proton NMR spectra provides further information on association of protein monomers. The region of the protein involved in folding, polymerization and substrate specificities is conservative in various species and we can surmise that it may have a specialized role in protein-lipid interactions in the myelin membrane. We suggest that the protein forms dimers across the cytoplasmic apposition during the formation of myelin. Estimates of the repulsive energies of interaction between approaching membranes suggest that some special mechanism of this kind is required to overcome the repulsive forces due to breakdown of water structure and electrostatic interaction.
D000818:Animals; D002417:Cattle; D004563:Electrochemistry; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D004676:Myelin Basic Protein / Q000502:physiology; D009186:Myelin Sheath / Q000254:growth & development* / Q000648:ultrastructure; D010743:Phospholipids / Q000502:physiology; D011487:Protein Conformation; D014867:Water
D004676:Myelin Basic Protein; D010743:Phospholipids; D014867:Water