Assembly and stability of nisin-Lipid II pores
Assembly and stability of nisin-Lipid II pores
复制标题
DOI：
10.1021/bi049476b
复制
发表时间：
2004-09-14
期刊：
影响因子：
2.9
通讯作者：
Breukink, E
中科院分区：
文献类型：
--
作者：
Hasper, HE;de Kruijff, B;Breukink, E
肽抗生素nisin是第一个报道的抗生素通过靶向孔形成杀死细菌的例子。nisin的特异性靶点是脂质II，这是细菌细胞壁合成的重要中间体。抗生素与脂质II的高亲和力结合随后是膜的快速渗透。本文利用芘荧光和圆二色性研究了nisin-脂质II孔复合物的组装和稳定性。我们证明了nisin利用膜中所有可用的脂质II分子形成孔复合物。孔复合物具有均匀的结构，由8个nisin和4个脂质II分子组成。此外，由于它们能够抵抗温和洗涤剂对膜环境的增溶作用，因此孔隙表现出显著的稳定性。用[N20P/M21P]nisin进行的类似实验表明，铰链区域对于组装成稳定的孔复合物至关重要。新的见解被用来提出nisin孔隙形成的精细模型。
The peptide antibiotic nisin was the first reported example of an antibiotic that kills bacteria via targeted pore formation. The specific target of nisin is Lipid II, an essential intermediate in the bacterial cell-wall synthesis. High-affinity binding of the antibiotic to Lipid II is followed by rapid permeabilization of the membrane. Here, we investigated the assembly and stability of nisin-Lipid II pore complexes by means of pyrene fluorescence and circular dichroism. We demonstrated that nisin uses all available Lipid II molecules in the membrane to form pore complexes. The pore complexes have a uniform structure and consist of 8 nisin and 4 Lipid II molecules. Moreover, the pores displayed a remarkable stability, because they were able to resist the solubilization of the membrane environment by mild detergents. Similar experiments with [N20P/M21P]nisin showed that the hinge region is essential for the assembly into stable pore complexes. The new insights were used to propose a refined model for nisin pore formation.