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Molecular basis for membrane selectivity of an antimicrobial peptide, magainin 2
K Matsuzaki1, K Sugishita, N Fujii
1Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Abstract:
Magainin peptides, isolated from Xenopus skin, kill bacteria by permeabilizing their cell membranes whereas they do not lyse erythrocytes. To elucidate the rationale for this membrane selectivity, we compared the effects of the membrane lipid composition and the transmembrane potential on the membrane-lytic power of magainin 2 with that of hemolytic melittin. The activity of magainin to zwitterionic phospholipids constituting the erythrocyte surface was extremely weak compared with that of melittin, and acidic phospholipids are necessary for effective action. The presence of sterols reduced the susceptibility of the membrane to magainin. The generation of an inside-negative transmembrane potential enhanced magainin-induced hemolysis. We can conclude that the absence of any acidic phospholipids on the outer monolayer and the abundant presence of cholesterol, combined with the lack of the transmembrane potential, contribute to the protection of erythrocytes from magainin's attack.
Insights
Magainin peptides kill bacteria by disrupting membranes but spare red blood cells. Erythrocyte protection stems from their lipid composition and lack of electrical potential, preventing magainin binding and lysis.
Area of Science:
- Biochemistry
- Molecular Biology
- Membrane Biophysics
Background:
- Magainin peptides from Xenopus skin exhibit potent antimicrobial activity by targeting bacterial membranes.
- Unlike their effect on bacteria, magainins do not lyse erythrocytes, suggesting specific membrane selectivity.
- Understanding this selectivity is crucial for developing magainin-based therapeutics.
Purpose of the Study:
- To elucidate the membrane selectivity of magainin 2 compared to hemolytic melittin.
- To investigate the influence of membrane lipid composition and transmembrane potential on magainin's lytic activity.
Main Methods:
- Comparative analysis of magainin 2 and melittin activity against model membranes with varying lipid compositions.
- Assessment of the role of zwitterionic and acidic phospholipids in magainin-induced membrane permeabilization.
- Evaluation of the impact of sterols and transmembrane potential on magainin's lytic power.
Main Results:
- Magainin 2 showed significantly weaker activity against zwitterionic phospholipids found on erythrocyte surfaces compared to melittin.
- Acidic phospholipids were essential for effective magainin action.
- Sterols, such as cholesterol, reduced membrane susceptibility to magainin.
- An inside-negative transmembrane potential enhanced magainin-induced hemolysis.
Conclusions:
- Erythrocytes are protected from magainin attack due to the absence of acidic phospholipids on their outer membrane leaflet.
- The abundance of cholesterol in erythrocyte membranes contributes to resistance against magainin.
- The lack of a significant transmembrane potential in erythrocytes further prevents magainin-induced lysis.