Lipid concentration effects on the amyloidogenic apoC-II(60-70) peptide: a computational study.
Molecular dynamics simulations were implemented to investigate the effects of phospholipid concentration on the conformation and dynamics of the amyloidogenic peptide apoC-II(60-70). The results showed a progressive reduction in the solvent accessible surface area of apoC-II(60-70) with increasing lipid concentration, accompanied by increased lipid-peptide interactions. Favorable peptide interaction sites with lipids were found to be the aromatic residues, Tyr63 and Phe67. The high stability of lipid-peptide contacts resulted in reduced conformational flexibility of the peptide. A significant change in the secondary structure of apoC-II(60-70) peptide was observed with increasing lipid concentration. At lower concentrations (1-3 lipids per peptide), the peptide adopted extended beta-strand conformations, caused by contacts with the lipids, which reduced the intramolecular interactions within the peptide. In contrast, a higher lipid concentration (4-6 lipids per peptide) had a restraining effect on the peptide's flexibility by trapping it in a particular conformation. Such behavior can be suggested as inhibiting fibril formation, because of the lipid-induced inability of the peptide to adopt fibril competent conformations. This finding complements our recent ThT fluorescence results, which revealed that the 4:1 lipid to peptide ratio is sufficient to cause fibril inhibition in apoC-II(60-70).
Todorova
Nevena
N
Applied Physics, School of Applied Sciences, RMIT University, Melbourne, Victoria, 3001, Australia.
Hung
Andrew
A
Yarovsky
Irene
I
D000595:Amino Acid Sequence; D053304:Apolipoprotein C-II / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D017433:Protein Structure, Secondary
D053304:Apolipoprotein C-II; D010455:Peptides; D010743:Phospholipids