Potent Macromolecule-Sized Poration of Lipid Bilayers by the Macrolittins, A Synthetically Evolved Family of Pore-Forming Peptides
Potent Macromolecule-Sized Poration of Lipid Bilayers by the Macrolittins, A Synthetically Evolved Family of Pore-Forming Peptides
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DOI：
10.1021/jacs.8b03026
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发表时间：
2018-05-23
影响因子：
15
通讯作者：
Hristova, Kalina
中科院分区：
文献类型：
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作者：
Li, Sijia;Kim, Sarah Y.;Hristova, Kalina
具有新功能的造孔肽在许多生物技术应用中具有潜在的应用价值。然而，成孔肽的序列-结构-功能关系还不够清楚，不足以支持合理的设计。因此，在这项工作中，我们利用合成分子进化来鉴定一类新的多肽，这些多肽在低肽浓度和中性pH条件下能够在合成脂泡中引起大分子穿孔。这些独特的26个残基的多肽，我们称之为大分子，从由两性离子PC脂类制成的脂双层囊泡中释放大分子，其肽与脂的比例低至1：1000，这一特性在已知的膜通透性多肽中几乎是前所未有的。大分子内酯以跨膜的α-螺旋形式存在。它们导致双分子层显著变薄，并在平面支撑的双分子层中形成大孔。这些多肽的高效力可能是因为它们通过需要多肽之间特定的静电相互作用的过程来稳定双层边缘的能力。
Pore-forming peptides with novel functions have potential utility in many biotechnological applications. However, the sequence-structure-function relationships of pore forming peptides are not understood well enough to empower rational design. Therefore, in this work, we used synthetic molecular evolution to identify a novel family of peptides that are highly potent and cause macromolecular poration in synthetic lipid vesicles at low peptide concentration and at neutral pH. These unique 26-residue peptides, which we call macrolittins, release macromolecules from lipid bilayer vesicles made from zwitterionic PC lipids at peptide to lipid ratios as low as 1:1000, a property that is almost unprecedented among known membrane permeabilizing peptides. The macrolittins exist as membrane-spanning a-helices. They cause dramatic bilayer thinning and form large pores in planar supported bilayers. The high potency of these peptides is likely due to their ability to stabilize bilayer edges by a process that requires specific electrostatic interactions between peptides.