Self-association of myelin basic protein: enhancement by detergents and lipids

Self-association of basic protein has been proposed to be of functional significance in central nervous system myelin. In aqueous solution this protein self-associates, previous data being consistent with the formation of dimers, which then undergo an indefinite isodesmic self-association [Smith, R. (1980) Biochemistry 19, 1826-1831]. As this protein is membrane bound in vivo, we have now examined the effects of amphiphiles on the self-association equilibria. Contrary to the expected effects, at low molar ratios dodecyl sulfate, deoxycholate, Triton X-100, and lysophosphatidylcholine increased protein intermolecular attraction. The anionic detergents led to partial precipitation even at 1:1 protein:detergent molar ratios whereas the zwitterionic lipid and the nonionic detergent exerted less pronounced effects. Sedimentation velocity and equilibrium measurements have been used to define quantitatively the effects of lysophosphatidylcholine. The sedimentation coefficient increases up to a lipid:protein ratio of 4:1 and then remains constant up to a ratio of 12:1. The sedimentation equilibrium data suggest that the mode of protein-protein interaction is the same as in the absence of lipid but with substantially increased association constants. The dimerization constant is increased from 1.20 X 10(2) M-1 to 1.0 X 10(3) M-1 and the isodesmic association constant from 3.4 X 10(4) M-1 to 1.2 X 10(5) M-1. The effects of detergents on myelin basic protein are compared with the effects on other proteins, and the implications for the state of the protein with myelin are discussed.