DIRECT DETERMINATION OF THE MEMBRANE AFFINITIES OF INDIVIDUAL AMINO-ACIDS

Amino acids have distinct lipid bilayer affinities which influence the insertion and topology of membrane-bound polypeptides and proteins. T o measure membrane affinities, 14 uncharged amino acids were introduce d individually at a guest site in a 25-residue peptide derived from th e membrane-binding presequence of yeast cytochrome c oxidase, and the peptides were labeled with a nitroxide spin-label. The free energies o f transfer from phospholipid bilayers to water (Delta Delta G(bilayer) ) were determined directly by examination of partitioning into phospho lipid bilayers using electron paramagnetic resonance. The Delta Delta G(bilayer) values are in agreement with hydrophobicities assessed from 1-octanol-water partitioning of N-acetyl amino acid amides [Fauchere, J.-L., & Pliska, V. (1983) fur. J, Med. Chem. 18, 369-375; Eisenberg, D,, & McLachlan, A. (1986) Nature 319, 199-203] and quantitatively de monstrate the role of the hydrophobic effect in membrane-protein inter actions.