Lins L, Ducarme P, Breukink E, Brasseur R
INSERM U10, Hôpital Bichat, 170 bd Ney, 75018, Paris, France.
Biochim Biophys Acta. 1999 Aug 20;1420(1-2):111-20. doi: 10.1016/s0005-2736(99)00090-5.
Nisin is a 34-residue lantibiotic widely used as food preservative. Its mode of action on the bacterial cytoplasmic membrane is unclear. It should form ion channels but a molecular description of the interaction between nisin and phospholipids is lacking. The interactions between nisin and a membrane and the influence of phospholipids are here analysed by molecular modelling. The NMR structures of nisin in a micellar environment were previously determined (Van den Hooven et al., Eur. J. Biochem. 235 (1996) 382-393) Those structures were used to start with. They were refined by running a Monte Carlo procedure at a model lipid/water interface. It was shown that nisin is adsorbing onto the interface, with its N-terminal moiety more deeply inserted in lipids than the C-end, indicating distinct hydrophobic properties of the N- and C-domains. Therefore, we suggest that the N-terminal part is implied in the insertion of nisin in lipids, while the C-terminal moiety could be involved in the initial interaction with the membrane surface. Modelling the interaction of nisin with different neutral or anionic phospholipids shows that it disturbs the lipid organisation. The disturbance is maximal with phosphatidylglycerol. In this system, nisin curves the surface of phosphatidylglycerol layer round suggesting it could induce micelle formation. This could be a preliminary step to pore formation. It suggests that phosphatidylglycerol could have a direct action on nisin insertion and on ion channel formation. Appearance of a curvature also agrees with the 'wedge model' proposed in the literature for the nisin pore formation.
乳酸链球菌素是一种由34个氨基酸残基组成的羊毛硫抗生素，广泛用作食品防腐剂。其对细菌细胞质膜的作用方式尚不清楚。它应该形成离子通道，但缺乏对乳酸链球菌素与磷脂之间相互作用的分子描述。本文通过分子建模分析了乳酸链球菌素与膜之间的相互作用以及磷脂的影响。先前已确定了乳酸链球菌素在胶束环境中的NMR结构（Van den Hooven等人，《欧洲生物化学杂志》235 (1996) 382 - 393），以此作为起始结构。通过在模型脂质/水界面运行蒙特卡罗程序对其进行了优化。结果表明，乳酸链球菌素吸附在界面上，其N端部分比C端更深入地插入脂质中，表明N域和C域具有不同的疏水特性。因此，我们认为N端部分参与了乳酸链球菌素插入脂质的过程，而C端部分可能参与了与膜表面的初始相互作用。对乳酸链球菌素与不同中性或阴离子磷脂相互作用的建模表明，它会扰乱脂质的组织。与磷脂酰甘油的干扰最大。在这个系统中，乳酸链球菌素使磷脂酰甘油层表面弯曲，表明它可能诱导胶束形成。这可能是形成孔道的初步步骤。这表明磷脂酰甘油可能对乳酸链球菌素的插入和离子通道的形成有直接作用。曲率的出现也与文献中提出的乳酸链球菌素孔道形成的“楔模型”一致。
