Self-association of helical peptides in a lipid environment.

Abstract

The self-association of two model transmembrane helical peptides, differing in their surface topography, was compared in mixed micelles containing 3-([3-cholamidopropyl]dimethylammonio)-1-propanesulfonate (CHAPS) and dimyristoylphosphatidylcholine (DMPC). One peptide, Ac-KKL24KK-amide (L24), has large, rotationally mobile leucine side chains and a relatively rough surface. The other peptide, Ac-KKLLLLLLAALLALLAALLALLLLLLKK-amide (L18A6), has a patch of small alanines on one side of the helix that forms a smooth surface. The aggregation state of the peptides was sampled by chemical cross-linking with bis-sulfosuccinimidyl suberate (B53). A monomer-aggregate association constant was obtained from the cross-linking results in the range of 2 x 10(5) M(-1) to 3 x I0(5) M(-1) for both peptides. Kinetics of formation of cross-linked dimers indicated that the ratio of dimerization constants for L18A6 to L24 was between 10 and 20. This suggests that the alanine patch contributes about 1.5 Kcal/mol more stabilization free energy to dimer formation of L18A6 compared to L24.