Modular analysis of hipposin, a histone-derived antimicrobial peptide consisting of membrane translocating and membrane permeabilizing fragments.
Modular analysis of hipposin, a histone-derived antimicrobial peptide consisting of membrane translocating and membrane permeabilizing fragments.
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DOI：
10.1016/j.bbamem.2014.04.010
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Elmore DE
中科院分区：
文献类型：
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作者：
Bustillo ME;Fischer AL;LaBouyer MA;Klaips JA;Webb AC;Elmore DE
抗菌肽作为传统抗生素的潜在替代品继续受到关注。海马蛋白是一种组蛋白衍生的抗菌肽（HDAP），以前从大西洋比目鱼中分离出来。虽然其对几种细菌菌株的效力已被证明，但其抗菌机制尚未被表征。这种肽的机制是特别有趣的考虑，因为完整的海马苷序列含有副溶血素和buforin II（BF 2）的序列，这两种其他已知的抗菌肽通过不同的抗菌机制发挥作用。当parasin通过诱导膜透化杀死细菌时，buforin II进入细胞而不引起显著的膜破坏，通过与细胞内核酸的相互作用伤害细菌。在这项研究中，我们使用了一个模块化的方法来表征hipposin和确定的parasin和buforin II片段在整个hipposin机制的作用。我们的研究结果表明，海马蛋白杀死细菌诱导膜透性，这种膜透性的N-末端副蛋白结构域的存在下，促进。缺乏parasin序列的部分海马苷不会引起膜透化，并且功能与buforin II更相似。我们还确定了海马蛋白的C-末端部分，HipC，是一种细胞穿透肽，很容易进入细菌细胞，但没有可测量的抗菌活性。HipC是第一个被鉴定的不杀死细菌或真核细胞的膜活性组蛋白片段。总之，这些结果不仅表征了海马蛋白，而且为考虑通过组合经由不同机制操作的肽而制成的嵌合肽的活性提供了有用的起点。
Antimicrobial peptides continue to garner attention as potential alternatives to conventional antibiotics. Hipposin is a histone-derived antimicrobial peptide (HDAP) that was previously isolated from Atlantic halibut. Though its potency against several bacterial strains has been documented, its antibacterial mechanism had not been characterized. The mechanism of this peptide is particularly interesting to consider since the full hipposin sequence contains the sequences of parasin and buforin II (BF2), two other known antimicrobial peptides that act via different antibacterial mechanisms. While parasin kills bacteria by inducing membrane permeabilization, buforin II enters cells without causing significant membrane disruption, harming bacteria through interactions with intracellular nucleic acids. In this study, we used a modular approach to characterize hipposin and determine the role of the parasin and buforin II fragments in the overall hipposin mechanism. Our results show that hipposin kills bacteria by inducing membrane permeabilization, and this membrane permeabilization is promoted by the presence of the N-terminal parasin domain. Portions of hipposin lacking the parasin sequence do not cause membrane permeabilization and function more similarly to buforin II. We also determined that the C-terminal portion of hipposin, HipC, is a cell-penetrating peptide that readily enters bacterial cells but has no measurable antimicrobial activity. HipC is the first membrane active histone fragment identified that does not kill bacterial or eukaryotic cells. Together, these results not only characterize hipposin but also provide a useful starting point for considering the activity of chimeric peptides made by combining peptides that operate via differing mechanisms.