Interactions of histatin 5 and histatin 5-derived peptides with liposome membranes: surface effects, translocation and permeabilization
Interactions of histatin 5 and histatin 5-derived peptides with liposome membranes: surface effects, translocation and permeabilization
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DOI：
10.1042/bj20031785
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发表时间：
2004-05-01
影响因子：
4.1
通讯作者：
Amerongen, AVN
中科院分区：
文献类型：
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作者：
den Hertog, AL;Sang, HWWF;Amerongen, AVN
许多阳离子抗菌肽，其中包括组蛋白5及其衍生多肽dhvar4和dhvar5，进入其靶细胞并与内部细胞器相互作用。关于抗菌肽跨膜转运的机制仍然存在疑问。我们利用脂质体模型研究了组蛋白5、dhvar4和dhvar5的膜结合、转位和膜扰动能力。尽管这些多肽的两亲性不同，但它们与脂质体结合得同样好，但它们的膜活性有显著差异：dhvar4的转位速度最快，其次是dhvar5，而组蛋白5的转位速度要低得多。钙黄绿素的释放程度也有相同的规律：dhvar4最高，dhvar5次之，组蛋白5几乎没有。dhvar5的易位和破坏作用似乎不是耦合的，因为易位发生的时间比钙黄绿素释放的时间长得多，在几分钟内结束。我们得出结论，多肽易位可以通过多肽-磷脂相互作用发生，这可能是抗菌肽进入细胞的一种机制。然而，在这个模型膜系统中，转移率比在酵母细胞中看到的要低得多。因此，很可能，至少对某些多肽来说，还涉及促进跨生物膜转位的额外特征。
A number of cationic antimicrobial peptides, among which are histatin 5 and the derived peptides dhvar4 and dhvar5, enter their target cells and interact with internal organelles. There still are questions about the mechanisms by which antimicrobial peptides translocate across the membrane. We used a liposome model to study membrane binding, translocation and membrane-perturbing capacities of histatin 5, dhvar4 and dhvar5. Despite the differences in amphipathic characters of these peptides, they bound equally well to liposomes, whereas their membrane activities differed remarkably: dhvar4 translocated at the fastest rate, followed by dhvar5, whereas the histatin 5 translocation rate was much lower. The same pattern was seen for the extent of calcein release: highest with dhvar4, less with dhvar5 and almost none with histatin 5. The translocation and disruptive actions of dhvar5 did not seem to be coupled, because translocation occurred on a much longer timescale than calcein release, which ended within a few minutes. We conclude that peptide translocation can occur through peptide-phospholipid interactions, and that this is a possible mechanism by which antimicrobial peptides enter cells. However, the translocation rate was much lower in this model membrane system than that seen in yeast cells. Thus it is likely that, at least for some peptides, additional features promoting the translocation across biological membranes are involved as well.