Biology & Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge, TN, 37831, USA.
Center for Structural Molecular Biology, Oak Ridge National Laboratory, Oak Ridge, TN, 37831, USA.
Sci Rep. 2017 Jun 16;7(1):3719. doi: 10.1038/s41598-017-03795-6.
Aurein 1.2 is a potent antimicrobial peptide secreted by frog Litoria aurea. As a short membrane-active peptide with only 13 amino acids in sequence, it has been found to be residing on the surface of lipid bilayer and permeabilizing bacterial membranes at high concentration. However, the detail at the molecular level is largely unknown. In this study, we investigated the action of Aurein 1.2 in charged lipid bilayers composed of DMPC/DMPG. Oriented Circular Dichroism results showed that the peptide was on the surface of lipid bilayer regardless of the charged lipid ratio. Only at a very high peptide-to-lipid ratio (~1/10), the peptide became perpendicular to the bilayer, however no pore was detected by neutron in-plane scattering. To further understand how it interacted with charged lipid bilayers, we employed Small Angle Neutron Scattering to probe lipid distribution across bilayer leaflets in lipid vesicles. The results showed that Aurein 1.2 interacted strongly with negatively charged DMPG, causing strong asymmetry in lipid bilayer. At high concentration, while the vesicles were intact, we found additional structure feature on the bilayer. Our study provides a glimpse into how Aurein 1.2 disturbs anionic lipid-containing membranes without pore formation.
Aurein 1.2 是一种由青蛙 Litoria aurea 分泌的强效抗菌肽。作为一种仅由 13 个氨基酸组成的短膜活性肽，它被发现存在于脂质双层的表面，并在高浓度下使细菌膜穿孔。然而，其在分子水平上的详细情况在很大程度上尚不清楚。在这项研究中，我们研究了 Aurein 1.2 在由 DMPC/DMPG 组成的带电脂质双层中的作用。定向圆二色性结果表明，无论带电脂质的比例如何，肽都位于脂质双层的表面。只有在非常高的肽-脂比（~1/10）下，肽才会垂直于双层，但中子面内散射未检测到孔。为了进一步了解它如何与带电脂质双层相互作用，我们使用小角中子散射来探测脂质囊泡中双层叶层之间的脂质分布。结果表明，Aurein 1.2 与带负电荷的 DMPG 强烈相互作用，导致脂质双层强烈不对称。在高浓度下，虽然囊泡保持完整，但我们在双层上发现了额外的结构特征。我们的研究提供了一个关于 Aurein 1.2 如何在不形成孔的情况下扰乱含阴离子脂质的膜的见解。
