Dependence on lipid structure of the coil-to-helix transition of bovine myelin basic protein.

In aqueous solution bovine myelin basic protein has a close-to-random coil structure that is partially transformed to helix on interaction with lipids. Circular dichroism spectra have been used to follow this conformational transition which, with phospholipids, decreases in the order phosphatidylglycerol, phosphatidic acid approximately equal to phospholipids, decreases in the order phosphatidylethanolamine. There appears to be a strong correlation between the extent of alpha-helix formation and the degree of penetration of the hydrophobic region of the bilayer, as assessed by other methods. Cholesterol mixed in bilayers with phosphatidylserine has little effect on the protein secondary structure. Although basic protein binds strongly to cerebroside and to cerebroside sulphate, two of the other major myelin lipids, the intrinsic chirality of these lipids precludes assessment of their effect on the protein conformation. No significant changes in the circular dichroism spectra accompany the protein association with either of the zwitterionic bilayer-forming lipids, phosphatidylethanolamine and phosphatidylcholine. This seems to exclude extensive penetration into bilayers of these lipids and hence to exclude appreciable hydrophobic interactions; on the other hand, it is argued that little evidence exists for ionic attractions to these lipids. The optical activity of peptides derived from the basic protein by cleavage at the 42-43 and 88-89 peptides bonds (with cathepsin D) and at the 115-116 bond (with a skatole derivative) has also been measured in an attempt to locate the helix-forming regions within the primary structure.