PDF(Pubmed)
Abstract：
Aurein 1.2 (aurein) is a short but active α-helical antimicrobial peptide discovered in Australian tree frogs (Litoria aurea). It shows inhibition on a broad spectrum of bacteria and cancer cells. With well-defined helicity, amphipathicity, and cationic charges, it readily binds to membranes and causes membrane change and disruption. This study provides details on how aurein interacts with charged lipid membranes by using neutron membrane diffraction (NMD) and neutron spin echo (NSE) spectroscopy on complex peptide-membrane systems. NMD provides higher resolution lipid bilayer structures than solution scattering. NMD revealed the peptide is mostly associated in the lipid headgroup region. Even at moderately high concentrations (e.g., peptide:lipid ratio of 1:30), aurein is located at the acyl chain-headgroup region without deep penetration into the hydrophobic acyl chain. However, it does reduce the elasticity of the membrane at that concentration, which was corroborated by the NSE results. Furthermore, NSE shows that aurein first softens the membrane, like many other α-helical peptides at low concentration, but then makes the membrane much more rigid, even without membrane pore formation. Combining our previous studies, the evidence shows that aurein at relatively low concentrations still modifies lipid distribution significantly and can cause membrane thinning and lateral segregation of charged lipids. At the same time, the membrane\'s mechanical properties are modified with much slower lipid diffusion. This suggests that aurein can attack the microbial membrane without the need to form membrane pores or disintegrate membranes; instead, it promotes the formation of domains at low concentration.
摘要：
Aurein1.2（aurein）是在澳大利亚树蛙（Litoriaaurea）中发现的一种短但有活性的α-螺旋抗菌肽。它显示对广谱细菌和癌细胞的抑制作用。具有明确定义的螺旋度，两亲性,和阳离子电荷，它很容易与膜结合，导致膜变化和破坏。这项研究通过在复杂的肽-膜系统上使用中子膜衍射（NMD）和中子自旋回波（NSE）光谱，提供了有关金黄色葡萄球菌如何与带电脂质膜相互作用的详细信息。NMD提供比溶液散射更高分辨率的脂质双层结构。NMD显示该肽主要在脂质头基区域相关。即使在中等高浓度下(例如，肽：脂质比例为1：30），金黄色葡萄球菌位于酰基链-头基区域，而不会深入疏水性酰基链。然而,在该浓度下，它确实会降低膜的弹性，NSE结果证实了这一点。此外，NSE显示aurein首先软化膜，像许多其他低浓度的α-螺旋肽一样，但是然后使薄膜更加坚硬，即使没有膜孔形成。结合我们之前的研究,证据表明，在相对较低的浓度下，aurein仍然会显著改变脂质分布，并可能导致膜变薄和带电脂质的横向分离。同时,膜的机械特性被改变，脂质扩散慢得多。这表明金黄色葡萄球菌可以攻击微生物膜，而不需要形成膜孔或崩解膜；相反，它促进低浓度域的形成。
