Institute of Biological Interfaces (IBG-2), Karlsruhe Institute of Technology (KIT), P.O. Box 3640, 76021 Karlsruhe, Germany.
Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, Hauz Khas, Delhi 110016, India.
Int J Mol Sci. 2021 Sep 21;22(18):10156. doi: 10.3390/ijms221810156.
A group of seven peptides from spider venom with diverse sequences constitute the latarcin family. They have been described as membrane-active antibiotics, but their lipid interactions have not yet been addressed. Using circular dichroism and solid-state N-NMR, we systematically characterized and compared the conformation and helix alignment of all seven peptides in their membrane-bound state. These structural results could be correlated with activity assays (antimicrobial, hemolysis, fluorescence vesicle leakage). Functional synergy was not observed amongst any of the latarcins. In the presence of lipids, all peptides fold into amphiphilic α-helices as expected, the helices being either surface-bound or tilted in the bilayer. The most tilted peptide, Ltc2a, possesses a novel kind of amphiphilic profile with a coiled-coil-like hydrophobic strip and is the most aggressive of all. It indiscriminately permeabilizes natural membranes (antimicrobial, hemolysis) as well as artificial lipid bilayers through the segregation of anionic lipids and possibly enhanced motional averaging. Ltc1, Ltc3a, Ltc4a, and Ltc5a are efficient and selective in killing bacteria but without causing significant bilayer disturbance. They act rather slowly or may even translocate towards intracellular targets, suggesting more subtle lipid interactions. Ltc6a and Ltc7, finally, do not show much antimicrobial action but can nonetheless perturb model bilayers.
一组来自蜘蛛毒液的具有不同序列的七种肽构成了 latarcin 家族。它们被描述为具有膜活性的抗生素，但它们的脂质相互作用尚未得到解决。使用圆二色性和固态 N-NMR，我们系统地描述并比较了所有七种肽在其结合膜状态下的构象和螺旋排列。这些结构结果可以与活性测定（抗菌、溶血、荧光囊泡渗漏）相关联。在任何 latarcins 中都没有观察到功能协同作用。在存在脂质的情况下，所有肽都按照预期折叠成两亲性 α-螺旋，螺旋要么是表面结合的，要么是倾斜在双层中的。最倾斜的肽 Ltc2a 具有一种新型的两亲性轮廓，带有卷曲螺旋样的疏水性条带，是所有肽中最具侵略性的。它通过阴离子脂质的分离和可能增强的运动平均，不加区分地渗透天然膜（抗菌、溶血）以及人工脂质双层。Ltc1、Ltc3a、Ltc4a 和 Ltc5a 能够有效地杀死细菌，但不会引起显著的双层干扰。它们的作用速度较慢，或者甚至可能向细胞内目标转移，这表明它们与脂质的相互作用更为微妙。最后，Ltc6a 和 Ltc7 虽然没有很强的抗菌作用，但仍然可以干扰模型双层。
