Functional independence of a peptide with the sequence of human apolipoprotein A-I central region

Previous results [J. Biol. Chem. 276 (2001) 16978] indicated that an apolipoprotein A-I (apoAI) central region swings away from lipid contact in discoidal high density lipoproteins (HDL), but it is able to penetrate into the bilayer of lipid vesicles. In this work, we have studied the interaction with lipid membranes of a synthetic peptide with the sequence of apoAI region between residues 77 and 120 (AI 77–120). Like apoAI, AI 77–120 binds to phospholipid vesicles and shows selectivity for cholesterol-containing membranes. Moreover, AI 77–120 promotes cholesterol desorption from membranes in a similar fashion as apoAI and can stimulate cholesterol efflux from Chinese hamster ovary cells. AI 77–120 has a considerable α-helical content in water solution, and its secondary structure is not largely modified after binding to membranes. Both apoA-I and AI 77–120 are oligomeric in the lipid-bound state, suggesting that dimerization of the central domain could be required for the membrane binding activity of apoA-I in HDL.