Two homologous apolipoprotein AI mimetic peptides. Relationship between membrane interactions and biological activity.
Two related 18-amino acid, class A, amphipathic helical peptides termed 3F-2 and 3F14 were chosen for this study. Although they have identical amino acid compositions and many similar biophysical properties, 3F-2 is more potent than 3F14 as an apolipoprotein AI mimetic peptide. The two peptides exhibit similar gross conformational properties, forming structures of high helical content on a membrane surface. However, the thermal denaturation transition of 3F-2 is more cooperative, suggesting a higher degree of oligomerization on the membrane. Both 3F-2 and 3F14 promote the segregation of cholesterol in membranes containing phosphatidylcholine and cholesterol, but 3F-2 exhibits a greater selectivity for partitioning into cholesterol-depleted regions of the membrane. Magic angle spinning/NMR studies indicate that the aromatic residues of 3F-2 are stacked in the presence of lipid. The aromatic side chains of this peptide also penetrate more deeply into membranes of phosphatidylcholine with cholesterol compared with 3F14. Using the fluorescent probe, 1,3-dipyrenylpropane, we monitored the properties of the lipid hydrocarbon environment. 3F-2 had a greater effect in altering the properties of the hydrocarbon region of the membrane. The results are consistent with our proposed model of the effect of peptide shape on the nature of the difference in peptide insertion into the bilayer.
Epand
Richard M
RM
Departments of Biochemistry and Biomedical Sciences and Chemistry, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. epand@mcmaster.ca
Epand
Raquel F
RF
Sayer
Brian G
BG
Datta
Geeta
G
Chaddha
Manjula
M
Anantharamaiah
G M
GM
D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000737:chemistry*; D055592:Biophysical Phenomena; D001703:Biophysics; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000378:metabolism*; D002498:Centrifugation; D002784:Cholesterol / Q000737:chemistry; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D005456:Fluorescent Dyes / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D011489:Protein Denaturation; D011522:Protons; D011721:Pyrenes / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D014364:Tryptophan / Q000737:chemistry
D016632:Apolipoprotein A-I; D005456:Fluorescent Dyes; D008024:Ligands; D008051:Lipid Bilayers; D008055:Lipids; D010455:Peptides; D010713:Phosphatidylcholines; D011522:Protons; D011721:Pyrenes; C035116:1,3-di-(1-pyrenyl)propane; D014364:Tryptophan; D002784:Cholesterol