La Trobe Institute for Molecular Science, La Trobe University, Australia.
Sci Rep. 2016 Nov 30;6:38184. doi: 10.1038/srep38184.
Membrane-disrupting antimicrobial peptides provide broad-spectrum defence against localized bacterial invasion in a range of hosts including humans. The most generally held consensus is that targeting to pathogens is based on interactions with the head groups of membrane lipids. Here we show that the action of LL-37, a human antimicrobial peptide switches the mode of action based on the structure of the alkyl chains, and not the head groups of the membrane forming lipids. We demonstrate that LL-37 exhibits two distinct interaction pathways: pore formation in bilayers of unsaturated phospholipids and membrane modulation with saturated phospholipids. Uniquely, the membrane modulation yields helical-rich fibrous peptide-lipid superstructures. Our results point at alternative design strategies for peptide antimicrobials.
膜破坏型抗菌肽为包括人类在内的多种宿主提供了针对局部细菌入侵的广谱防御。人们普遍认为，靶向病原体是基于与膜脂质头基的相互作用。在这里，我们表明，人抗菌肽 LL-37 的作用方式取决于烷基链的结构，而不是形成膜的脂质的头基。我们证明 LL-37 表现出两种不同的相互作用途径：不饱和磷脂双层中的孔形成和与饱和磷脂的膜调节。独特的是，膜调节产生富含螺旋的纤维状肽-脂质超结构。我们的结果指出了抗菌肽的替代设计策略。
