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 alpha-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.
Toledo
Juan Domingo
JD
Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP)-Consejo Nacional de Investigaciones Científicas y Técnicas / Universidad Nacional de La Plata, Facultad de Ciencias Médicas, Calles 60 y 120, 1900 La Plata, Argentina.
Prieto
Eduardo Daniel
ED
Gonzalez
Marina Cecilia
MC
Soulages
José Luis
JL
Garda
Horacio Alberto
HA
D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry*; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008027:Light; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013997:Time Factors
D016632:Apolipoprotein A-I; D008055:Lipids; D010455:Peptides; D002784:Cholesterol