Cecropins are positively charged antibacterial peptides that act by permeating the membrane of susceptible bacteria. To gain insight into the mechanism of membrane permeation, the secondary structure and the orientation within phospholipid membranes of the mammalian cecropin P1 (CecP) was studied using attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and molecular dynamics simulations. The shape and frequency of the amide I and II absorption peaks of CecP within acidic PE/PG multibilayers (phosphatidylethanolamine/phosphatidylglycerol) in a 7:3 (w/w) ratio (a phospholipid composition similar to that of many bacterial membranes), indicated that the peptide is predominantly alpha-helical. Polarized ATR-FTIR spectroscopy was used to determine the orientation of the peptide relative to the bilayer normal of phospholipid multibilayers. The ATR dichroic ratio of the amide I band of CecP peptide reconstituted into oriented PE/PG phospholipid membranes indicated that the peptide is preferentially oriented nearly parallel to the surface of the lipid membranes. A similar secondary structure and orientation were found when zwitterionic phosphatidylcholine phospholipids were used. The incorporation of CecP did not significantly change the order parameters of the acyl chains of the multibilayer, further suggesting that CecP does not penetrate the hydrocarbon core of the membranes. Molecular dynamics simulations were used to gain insight into possible effects of transmembrane potential on the orientation of CecP relative to the membrane. The simulations appear to confirm that CecP adopts an orientation parallel to the membrane surface and does not insert into the bilayer in response to a cis positive transmembrane voltage difference. Taken together, the results further support a "carpet-like" mechanism, rather than the formation of transmembrane pores, as the mode of action of CecP. According to this model, formation of a layer of peptide monomers on the membrane surface destablizes the phospholipid packing of the membrane leading to its eventual disintegration.

中文翻译：

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哺乳动物抗菌肽cecropin P1在磷脂膜内的结构和方向。

天蚕素是带正电荷的抗菌肽，可透过易感细菌的膜渗透。为了深入了解膜的渗透机制，使用衰减全反射傅里叶变换红外光谱（ATR-FTIR）光谱和分子动力学模拟研究了哺乳动物cecropin P1（CecP）的二级结构和磷脂膜内的取向。表明酸性PE / PG双层（磷脂酰乙醇胺/磷脂酰甘油）中CecP的酰胺I和II的CecP吸收峰的形状和频率（w / w）为7：3（w / w）（与许多细菌膜相似的磷脂组成）该肽主要是α-螺旋。使用极化的ATR-FTIR光谱确定肽相对于磷脂双层的正常双层的方向。重构为定向的PE / PG磷脂膜的CecP肽的酰胺I带的ATR二向色比表明，该肽优先定向为几乎与脂质膜的表面平行。当使用两性离子磷脂酰胆碱磷脂时，发现相似的二级结构和取向。CecP的并入不会显着改变多层双层的酰基链的有序参数，进一步表明CecP不会穿透膜的烃核。使用分子动力学模拟来深入了解跨膜电位对CecP相对于膜的取向的可能影响。模拟似乎证实了CecP采取平行于膜表面的方向，并且不响应顺式正跨膜电压差而插入双层中。两者合计，结果进一步支持“地毯状”机制，而不是跨膜孔的形成，作为CecP的作用方式。根据该模型，在膜表面上形成肽单体层破坏了膜的磷脂堆积，导致其最终崩解。而不是跨膜孔的形成，而是CecP的作用方式。根据该模型，在膜表面上形成肽单体层破坏了膜的磷脂堆积，导致其最终崩解。而不是跨膜孔的形成，而是CecP的作用方式。根据该模型，在膜表面上形成肽单体层破坏了膜的磷脂堆积，导致其最终崩解。