The Plasticins: Membrane Adsorption, Lipid Disorders, and Biological Activity

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• 作者：Chahrazade El Amri ; Claire Lacombe ; Karel Zimmerman ; Ali Ladram ; Mohamed Amiche ; Pierre Nicolas ; Francine Bruston
• 刊名：Biochemistry
• 出版年：2006
• 出版时间：December 5, 2006
• 年：2006
• 卷：45
• 期：48
• 页码：14285 - 14297
• 全文大小：426K
• 年卷期：v.45,no.48(December 5, 2006)
• ISSN：1520-4995

文摘

The present study investigates the relationships between structural polymorphism, adsorptiononto membrane mimetic support, lipid disturbance, and biological activity of bactericidal 23-residue, glycine-leucine-rich dermaseptin orthologues from the Phyllomedusinae frog skin, the "plasticins". Biologicalactivities were evaluated using the membrane models DMPG (1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol) for prokaryotic membranes and DMPC (1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine) foreukaryotic membranes. We performed a conformational analysis of plasticins by molecular simulationsand spectroscopic methods and analyzed phospholipid perturbations by infrared spectroscopy. Adsorptiononto synthetic model membranes was quantified by surface plasmon resonance. Biological assays includingantimicrobial and membrane potential-dissipating activities, together with hemolytic tests and imaginganalysis of cytotoxicity, were carried out to clarify the peptide-membrane interactions. Two major groupswere distinguished: (i) Neutral plasticins revealed the presence of strong -structures with the zwitterionicor anionic phospholipid vesicles. They were weakly adsorbed in the range of antibacterial activityconcentrations (micromolar). Nevertheless, for millimolar concentrations, they caused perturbations atthe interface peptide-DMPG vesicles and in the bilayer alkyl chains, suggesting insertion into bacterialmembranes. (ii) Cationic plasticins revealed multiple conformational transitions, including destabilizedhelix states, -structures, and disordered states. Peptide-lipid complex densities depended on hydrophobicbond strengths. The most soluble cationic plasticins were strongly adsorbed, with stable peptide-lipidinteractions inducing noticeable perturbations of bilayer alkyl chains, pointing out possible insertion intobacterial membranes. In contrast, cytotoxic plasticins were less adsorbed, with less stable peptide-lipidinteractions causing membrane dehydration, formation of peptide-membrane hydrogen bonds, and littledisturbances of lipid alkyl chains. These characteristics could be compatible with their putative action onintracellular targets leading to apoptosis.