Basañez Gorka, Shinnar Ann E, Zimmerberg Joshua
Unidad de Biofísica (Centro Mixto UPV/CSIC), y Departamento de Bioquímica y Biología Molecular, Universidad del Pais Vasco (UPV/EHU), P.O. Box 644, 48080 Bilbao, Spain.
FEBS Lett. 2002 Dec 4;532(1-2):115-20. doi: 10.1016/s0014-5793(02)03651-7.
Hagfish intestinal antimicrobial peptides (HFIAPs) are a family of polycationic peptides exhibiting potent, broad-spectrum bactericidal activity. In an attempt to unravel the mechanism of action of HFIAPs, we have studied their interaction with model membranes. Synthetic HFIAPs selectively bound to liposomes mimicking bacterial membranes, and caused the release of vesicle-encapsulated fluorescent markers in a size-dependent manner. In planar lipid bilayer membranes, HFIAPs induced erratic current fluctuations and reduced membrane line tension according to a general theory for lipidic pores, suggesting that HFIAP pores contain lipid molecules. Consistent with this notion, lipid transbilayer redistribution accompanied HFIAP pore formation, and membrane monolayer curvature regulated HFIAP pore formation. Based on these studies, we propose that HFIAPs kill target cells, at least in part, by interacting with their plasma membrane to induce formation of lipid-containing pores. Such a membrane-permeabilizing function appears to be an evolutionarily conserved host-defense mechanism of antimicrobial peptides.
盲鳗肠道抗菌肽（HFIAPs）是一类具有强大广谱杀菌活性的聚阳离子肽。为了阐明HFIAPs的作用机制，我们研究了它们与模型膜的相互作用。合成的HFIAPs选择性地结合模拟细菌膜的脂质体，并以尺寸依赖的方式导致囊泡包裹的荧光标记物释放。在平面脂质双分子层膜中，根据脂质孔的一般理论，HFIAPs诱导不规则的电流波动并降低膜线张力，这表明HFIAP孔包含脂质分子。与此观点一致，脂质跨双分子层重新分布伴随着HFIAP孔的形成，并且膜单层曲率调节HFIAP孔的形成。基于这些研究，我们提出HFIAPs至少部分地通过与其质膜相互作用以诱导含脂质孔的形成来杀死靶细胞。这种膜通透功能似乎是抗菌肽在进化上保守的宿主防御机制。
