The activity of the amphipathic peptide delta-lysin correlates with phospholipid acyl chain structure and bilayer elastic properties - PubMed (original) (raw)
The activity of the amphipathic peptide delta-lysin correlates with phospholipid acyl chain structure and bilayer elastic properties
Antje Pokorny et al. Biophys J. 2008.
Abstract
Release of lipid vesicle content induced by the amphipathic peptide delta-lysin was investigated as a function of lipid acyl chain length and degree of unsaturation for a series of phosphatidylcholines. Dye efflux and peptide binding were examined for three homologous lipid series: di-monounsaturated, di-polyunsaturated, and asymmetric phosphatidylcholines, with one saturated and one monounsaturated acyl chain. Except for the third series, peptide activity correlated with the first moment of the lateral pressure profile, which is a function of lipid acyl chain structure. In vesicles composed of asymmetric phosphatidylcholines, peptide binding and dye efflux are enhanced compared to symmetric, unsaturated lipids with similar pressure profiles. We attribute this to the entropically more favorable interaction of delta-lysin with partially saturated phospholipids. We find that lipid acyl chain structure has a major impact on the activity of delta-lysin and is likely to be an important factor contributing to the target specificity of amphipathic peptides.
Figures
FIGURE 1
CF efflux induced by _δ_-lysin (0.5 _μ_M) for a series of di-monounsaturated PCs: di14:1PC (dashed line), di16:1PC (solid line), di18:1PC (dotted line), and di20:1PC (_dashed_-dotted line). The lipid concentration in all experiments was 50 _μ_M.
FIGURE 2
The average time constant (τ) for CF release induced by _δ_-lysin from lipid vesicles as a function of the number of double bonds in di18:_x_PC, where x represents the number of double bonds. Each error bar represents the standard deviation of a minimum of five individual traces. In the kinetic experiments, the peptide concentration was 0.5 _μ_M and the lipid concentration was 50 _μ_M.
FIGURE 3
The average time constant (τ) for CF release induced by _δ_-lysin as a function of the stretching modulus, _K_A, for POPC (∇), SOPC (Δ), di18:3PC (◊), di18:2PC (□), di18:1PC (♦), and di22:1PC (•). Each vertical error bar represents the standard deviation of a minimum of five individual kinetic traces. The peptide concentration in the dye release experiments was 0.5 _μ_M and the lipid concentration was 50 _μ_M. The values for _K_A and their standard deviations were taken from Rawicz et al. (39).
FIGURE 4
The average time constant for CF release induced by _δ_-lysin from lipid vesicles as a function of the bending modulus, _k_c. Solid symbols correspond to the di-monounsaturated PCs di16:1PC (▸), di18:1PC (♦), di20:1PC (◂), and di22:1PC (•). Open square symbols correspond to the di-polyunsaturated PCs di18:3PC (◊) and di18:2PC (□). Open triangular symbols correspond to POPC (∇) and SOPC (Δ). Each vertical error bar represents the standard deviation of a minimum of five individual kinetic traces. The dashed line is a linear fit to the data for the di-monounsaturated PCs (solid symbols). The peptide concentration in the dye release experiments was 0.5 _μ_M and the lipid concentration was 50 _μ_M. The values for _k_c and their standard deviations were taken from Rawicz et al. (39) and Kučerka et al. (52).
FIGURE 5
The average time constant for CF release induced by _δ_-lysin from lipid vesicles as a function of hydrophobic thickness, h. Solid symbols correspond to the di-monounsaturated PCs di14:1PC (▪), di16:1PC (▸), di18:1PC (♦), di20:1PC (◂), and di22:1PC (•). Open square symbols correspond to the di-polyunsaturated PCs di18:3PC (◊) and di18:2PC (□). Open triangular symbols correspond to POPC (∇) and SOPC (Δ). Each error bar represents the standard deviation of a minimum of five individual kinetic traces. The dashed line is a linear fit to the data for the di-monounsaturated PCs (solid circles). The peptide concentration in the dye release experiments was 0.5 _μ_M and the lipid concentration was 50 _μ_M. The values for h were taken from Hinderliter et al. (64).
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