Mechanism of leakage of phospholipid vesicle contents induced by the peptide GALA
| Autor: | Roberta A. Parente, Shlomo Nir, Francis C. Szoka |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
chemistry.chemical_classification
Liposome Chromatography Vesicle Bilayer Lipid Bilayers Molecular Sequence Data Molecular Conformation Synthetic membrane Phospholipid Peptide Biological membrane Hydrogen-Ion Concentration Biochemistry Permeability Kinetics Structure-Activity Relationship chemistry.chemical_compound chemistry Liposomes Biophysics Computer Simulation Amino Acid Sequence Peptides Lipid bilayer |
| Zdroj: | Biochemistry. 29:8720-8728 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi00489a031 |
| Popis: | The synthetic, amphipathic peptide GALA undergoes a pH-dependent conformational change and induces leakage of contents from large unilamellar phosphatidylcholine vesicles when in a helical conformation. The kinetics of this process have been investigated over a wide range of pH and lipid and peptide concentrations. Leakage from lipid vesicles is rapidly initiated (within 2 s) when the pH is lowered below 6 and is rapidly terminated when the pH is raised to 7.5. The leakage shows a selectivity to the size of the entrapped molecules and occurs by an all or none mechanism; vesicles either leak or retain all of their contents. Using this experimental data, we have developed a mathematical description of the kinetics of leakage induced by GALA. This model assumes that GALA becomes incorporated into the vesicle bilayer and aggregates to form a pore. Leakage occurs when a critical number of peptides assemble into a supramolecular aggregate in the bilayer. Leakage curves generated at lipid/peptide ratios ranging from 500/1 to 30000/1 can be well described by this formalism. On the basis of the results and the model, we suggest that GALA forms a transbilayer channel composed of 8-12 monomers. The channel diameter ranges from 5 to 10 A. To the best of our knowledge, this is the first model that can predict the leakage kinetics of solutes entrapped in lipid vesicles induced by a pore-forming peptide. The analysis may be of general use in defining the kinetics and state of aggregation of similarly acting peptides and proteins which form multimeric assemblies in membranes. |
| Databáze: | OpenAIRE |
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