Membrane pores induced by magainin
Membrane pores induced by magainin
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DOI：
10.1021/bi9620621
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发表时间：
1996-10-29
期刊：
影响因子：
2.9
通讯作者：
Huang, HW
中科院分区：
文献类型：
--
作者：
Ludtke, SJ;He, K;Huang, HW
Magainin 存在于非洲爪蟾的皮肤中，属于一大类抗菌肽，通过透化细胞质膜来杀死细菌，但不会裂解真核细胞。 23 个残基的肽已被证明在与膜结合时形成两亲性螺旋。然而，其分子作用机制一直存在争议。定向圆二色性已在高肽浓度下检测到垂直于膜平面定向的螺旋magainin，但拉曼、荧光、差示扫描量热法和NMR都表明该肽与脂质双层的头基相关。在这里，我们表明，仅当大部分肽垂直于膜取向时，中子面内散射才能检测到膜中 magainin 2 形成的孔。毛孔几乎是阿拉甲辛毛孔的两倍。基于面内散射数据，我们提出了一个环形（或虫洞）模型，该模型与阿拉甲星的桶板模型不同，因为脂质像环面的内部一样向后弯曲。弯曲需要双层头组区域的横向膨胀。 Magainin单体在膨胀区域起到填料的作用，从而稳定孔隙。该分子构型与所有已发表的magainin 数据一致。
Magainin, found in the skin of Xenopus laevis, belongs to a broad class of antimicrobial peptides which kill bacteria by permeabilizing the cytoplasmic membrane but do not lyse eukaryotic cells. The 23-residue peptide has been shown to form an amphiphilic helix when associated with membranes. However, its molecular mechanism of action has been controversial. Oriented circular dichroism has detected helical magainin oriented perpendicular to the plane of the membrane at high peptide concentrations, but Raman, fluorescence, differential scanning calorimetry, and NMR all indicate that the peptide is associated with the head groups of the lipid bilayer. Here we show that neutron in-plane scattering detects pores formed by magainin 2 in membranes only when a substantial fraction of the peptide is oriented perpendicular to the membrane. The pores are almost twice as large as the alamethicin pores. On the basis of the in-plane scattering data, we propose a toroidal (or wormhole) model, which differs from the barrel-stave model of alamethicin in that the lipid bends back on itself like the inside of a torus. The bending requires a lateral expansion in the head group region of the bilayer. Magainin monomers play the role of fillers in the expansion region thereby stabilizing the pore. This molecular configuration is consistent with all published magainin data.