An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation

An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation
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DOI:
10.1021/bi960016v
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发表时间:
1996-09-03
期刊:
影响因子:
2.9
通讯作者:
Miyajima, K
Miyajima, K
中科院分区:
生物学3区
文献类型:
--
作者:
Matsuzaki, K;Murase, O;Miyajima, K

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通过使用荧光脂质,即,阴离子N-(7-硝基苯-2-氧杂-1,3-二氮唑-4-基)二棕榈酰-L-α-磷脂酰乙醇胺(NBD-PE),1-油酰-2-[12-((7-硝基苯并-2-氧杂-1,3-二氮唑-4-基)-氨基)十二烷酰基]-L-α-磷脂酸(C-12-NBD-PA),1-油酰基-2-[12-((7-硝基苯-2-氧杂-1,3-二唑-4-基)-氨基)十二烷酰基]-L-α-磷脂酰-L-丝氨酸(C-12-NBD-PS)和两性离子1-棕榈酰基-2-[6-((7-硝基苯并-2-氧杂-1,3-二唑-4-基)氨基)己酰基]-L-α-磷脂酰胆碱(C-6-NBD-PC)。它们在30摄氏度下不存在肽的固有触发半衰期为1.1小时,约1.5小时。大约7小时。8天和>2天。这种肽将荧光脂质的半衰期加快到几分钟。此外,翻转与膜透化和肽易位偶联[Matsuzaki,K.,Murase,O.,Fujii,N.,& Miyajima,K.(1995)Biochemistry,34,6521-6526],表明孔介导的翻转。翻转率与初始标签条件(外瓣叶标签或内瓣叶标签)无关。根据这些结果,提出了一个模型,其中脂质通过沿着由肽和脂质组成的孔壁的侧向扩散而跨膜移位。一个简单的理论计算可以解释耦合的触发器与透化。
The effect of an antimicrobial peptide, magainin 2, on the flip-flop rates of phospholipids was investigated by use of fluorescent lipids, i.e., anionic N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)dipalmitoyl-L-alpha-phosphatidylethanolamine (NBD-PE), 1-oleoyl-2-[12-((7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino)dodecanoyl]-L-alpha-phosphatidic acid (C-12-NBD-PA), 1-oleoyl-2-[12-((7-nitrobenz-2-oxa-1,3-diazole-4-yl)-amino)dodecanoyl]-L-alpha-phosphatidyl-L-serine (C-12-NBD-PS), and zwitterionic 1-palmitoyl-2-[6-((7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)caproyl]-L-alpha-phosphatidylcholine (C-6-NBD-PC). Their intrinsic flip-flop half-lives at 30 degrees C in the absence of the peptide were 1.1 h, ca. 7 h, ca. 8 days, and >2 days, respectively. The peptide accelerated the flip-flop half-lives of the fluorescent lipids to an order of minutes. Furthermore, the flip-flop was coupled with the membrane permeabilization and the peptide translocation [Matsuzaki, K., Murase, O., Fujii, N., & Miyajima, K. (1995) Biochemistry, 34, 6521-6526], suggesting pore-mediated flip-flop. The flip-flop rate was independent of the initial labeling conditions (outer leaflet label or inner leaflet label). From these results, a model was proposed, in which the lipids translocate across the membrane by lateral diffusion along the wall of the pores composed of the peptides and the lipids. A simple theoretical calculation could explain the coupling of the flip-flop with the permeabilization.