Magainin 2 Revisited: A Test of the Quantitative Model for the All-or-None Permeabilization of Phospholipid Vesicles
Magainin 2 Revisited: A Test of the Quantitative Model for the All-or-None Permeabilization of Phospholipid Vesicles
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DOI：
10.1016/j.bpj.2008.09.017
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发表时间：
2009-01-07
影响因子：
3.4
通讯作者：
Almeida, Paulo F. F.
中科院分区：
文献类型：
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作者：
Gregory, Sonia M.;Pokorny, Antje;Almeida, Paulo F. F.
我们最近提出的抗菌肽cecropin A的全或无动力学模型在这里进行了magainin 2的测试。在磷脂酰胆碱(PC)/磷脂酰甘油（PG） 50:50和70:30的混合物中，脂质囊泡中内容物的释放以全有或无的方式发生，PC/PG 50:50和70:30之间的差异主要归因于结合的差异，这是独立确定的，PC/PG 50:50比70:30大20倍。只有一个可变参数0，对应于孔开闭率的比值，用于拟合这两种混合物的染料释放动力学，多肽/脂质比例范围为1:25至1:20 00。然而，与几乎保持不变的天蚕素A不同，当PG含量从30%增加到50%时，0增加了5倍。因此，magainin 2对阴离子脂质含量比cecropin A更敏感。但总体而言，magainin在这些脂质混合物中遵循与cecropin A相同的全或无动力学模型，只是参数值略有不同。当PG含量降至20 mol %时，染料释放率很低；其机制似乎发生了变化，并与分级动力学模型相一致。我们认为这种肽可能会诱导PG结构域的形成。在这两种机制中，都不会发生肽寡聚化，而且锰酸钠催化染料释放的过程与它在膜上的浓度成正比，处于一种我们称之为孔的肽状态。我们设想这种结构是一种混沌或随机类型的孔隙，涉及脂质和肽，而不是一个明确的，肽衬里的通道。
The all-or-none kinetic model that we recently proposed for the antimicrobial peptide cecropin A is tested here for magainin 2. In mixtures of phosphatidylcholine (PC)/phosphatidylglycerol (PG) 50:50 and 70:30, release of contents from lipid vesicles occurs in an all-or-none fashion and the differences between PC/PG 50:50 and 70:30 can be ascribed mainly to differences in binding, which was determined independently and is similar to 20 times greater to PC/PG 50:50 than to 70:30. Only one variable parameter, 0, corresponding to the ratio of the rates of pore opening to pore closing, is used to fit dye release kinetics from these two mixtures, for several peptide/lipid ratios ranging from 1:25 to 1:200. However, unlike for cecropin A where it stays almost constant, 0 increases five times as the PG content of the vesicles increases from 30 to 50%. Thus, magainin 2 is more sensitive to anionic lipid content than cecropin A. But overall, magainin follows the same all-or-none kinetic model as cecropin A in these lipid mixtures, with slightly different parameter values. When the PG content is reduced to 20 mol %, dye release becomes very low; the mechanism appears to change, and is consistent with a graded kinetic model. We suggest that the peptide may be inducing formation of PG domains. In either mechanism, no peptide oligomerization occurs and magainin catalyzes dye release in proportion to its concentration on the membrane in a peptide state that we call a pore. We envision this structure as a chaotic or stochastic type of pore, involving both lipids and peptides, not a well-defined, peptide-lined channel.