Afonin Sergii, Glaser Ralf W, Sachse Carsten, Salgado Jesús, Wadhwani Parvesh, Ulrich Anne S
Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), POB 3640, 76021 Karlsruhe, Germany.
Institute of Biochemistry and Biophysics, Friedrich-Schiller-Universität Jena, Hans-Knöll-Str. 2, 07745 Jena, Germany.
Biochim Biophys Acta. 2014 Sep;1838(9):2260-8. doi: 10.1016/j.bbamem.2014.03.017. Epub 2014 Mar 31.
Many amphiphilic antimicrobial peptides permeabilize bacterial membranes via successive steps of binding, re-alignment and/or oligomerization. Here, we have systematically compared the lipid interactions of two structurally unrelated peptides: the cyclic β-pleated gramicidin S (GS), and the α-helical PGLa. (19)F NMR was used to screen their molecular alignment in various model membranes over a wide range of temperatures. Both peptides were found to respond to the phase state and composition of these different samples in a similar way. In phosphatidylcholines, both peptides first bind to the bilayer surface. Above a certain threshold concentration they can re-align and immerse more deeply into the hydrophobic core, which presumably involves oligomerization. Re-alignment is most favorable around the lipid chain melting temperature, and also promoted by decreasing bilayer thickness. The presence of anionic lipids has no influence in fluid membranes, but in the gel phase the alignment states are more complex. Unsaturated acyl chains and other lipids with intrinsic negative curvature prevent re-alignment, hence GS and PGLa do not insert into mixtures resembling bacterial membranes, nor into bacterial lipid extracts. Cholesterol, which is present in high concentrations in animal membranes, even leads to an expulsion of the peptides from the bilayer and prevents their binding altogether. However, a very low cholesterol content of 10% was found to promote binding and re-alignment of both peptides. Overall, these findings show that the ability of amphiphilic peptides to re-align and immerse into a membrane is determined by the physico-chemical properties of the lipids, such as spontaneous curvature. This idea is reinforced by the remarkably similar behavior observed here for two structurally unrelated molecules (with different conformation, size, shape, charge), which further suggests that their activity at the membrane level is largely governed by the properties of the constituent lipids, while the selectivity towards different cell types is additionally ruled by electrostatic attraction between peptide and cell surface. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
许多两亲性抗菌肽通过结合、重新排列和/或寡聚化的连续步骤使细菌膜通透化。在此，我们系统地比较了两种结构不相关的肽的脂质相互作用：环状β-折叠短杆菌肽S（GS）和α-螺旋PGLa。利用（19）F核磁共振来筛选它们在很宽温度范围内在各种模型膜中的分子排列。发现这两种肽对这些不同样品的相态和组成的响应方式相似。在磷脂酰胆碱中，两种肽首先结合到双层表面。高于一定阈值浓度时，它们可以重新排列并更深地浸入疏水核心，这可能涉及寡聚化。重新排列在脂质链熔化温度附近最有利，并且也受到双层厚度减小的促进。阴离子脂质的存在在流体膜中没有影响，但在凝胶相中排列状态更复杂。不饱和酰基链和其他具有固有负曲率的脂质会阻止重新排列，因此GS和PGLa不会插入类似于细菌膜的混合物中，也不会插入细菌脂质提取物中。在动物膜中高浓度存在的胆固醇甚至会导致肽从双层中排出并完全阻止它们的结合。然而，发现极低的10%胆固醇含量会促进两种肽的结合和重新排列。总体而言，这些发现表明两亲性肽重新排列并浸入膜中的能力由脂质的物理化学性质决定，例如自发曲率。此处观察到的两种结构不相关分子（具有不同构象、大小、形状、电荷）的显著相似行为强化了这一观点，这进一步表明它们在膜水平的活性在很大程度上由组成脂质的性质决定，而对不同细胞类型的选择性还由肽与细胞表面之间的静电吸引决定。本文是名为：界面活性肽和蛋白质的特刊的一部分。客座编辑：威廉·C·温姆利和卡利娜·赫里斯托娃。
