Conformational properties of central nervous system myelin basic protein, β‐endorphin, and β‐lipotropin in water and in the presence of anionic lipids

Abstract

Conformational properties have been examined for three proteins which are disordered when dissolved in water but become partially ordered in the presence of anionic lipids. The three proteins, which play important roles in the central nervous system, are myelin basic protein, β‐endorphin, and β‐lipotropin. When evaluated using matrix methods, the helical content of each protein is predicted to be vanishingly small in water, in agreement with experiment. Unperturbed root‐mean‐square radii of gyration are also evaluated for these proteins in water using generator matrices, which have seen wide application to synthetic polymers. Agreement between computed and measured dimensions is found to be excellent. Having successfully described the conformations of myelin basic protein, β‐endorphin, and β‐lipotropin in water, attention is then directed to the changes induced upon interaction with anionic lipids or detergents. Computations predict an increase in helical content, with numerical results being in quite good agreement with experimental observations using several anionic lipids. Examination of the helix‐propagation‐probability profiles reveals an interesting feature of regions where this probability is high. When folded into a α‐helix, these regions show one surface where the only side chains are hydrophobic. Charged side chains (with positive charges predominating) are found on the other surface of the helical segment. The arrangement of side chains on these helices is thus well suited to promote favorable interactions with a membrane containing anionic lipids. Examples of the occurrence of these helices are provided by amino acid residues 13–25 and 130–157 in myelin basic protein and residues 17–29 in β‐endorphin.