Conformations and Dynamic Transitions of a Melittin Derivative in Lipid Bilayer
Conformations and Dynamic Transitions of a Melittin Derivative in Lipid Bilayer
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蜂毒肽衍生物在脂质双层中的构象和动态转变
DOI：
10.1016/j.bpj.2017.11.2505
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发表时间：
2018
影响因子：
3.4
通讯作者：
King, Gavin M.
中科院分区：
文献类型：
--
作者：
Pittman, Anna E.;King, Gavin M.
MelP 5是一种亲脂性肽，具有独特的物理性质，包括在低浓度下产生大而稳定的孔的能力。自组装成跨膜孔使得从蜂毒的主要毒性组分系统地进化而来的MelP 5成为未来在制药竞技场中应用的有希望的候选者，因为它提供了强大的药物递送机制。尽管具有重要意义，但关于MelP 5在结合后重塑脂质双层的机制知之甚少。在这里，我们通过原子力显微镜成像证明MelP 5以两种方式之一与脂双层相互作用：表面结合，导致双层变薄，或插入膜中，产生孔隙。双层的变薄被测量为在双层的上小叶下方<0.4nm，并且是孔形成的先决条件。孔隙具有许多稳定的尺寸，其中一些相当大。例如，约20%的孔表现出47+/-19.8nm2的足迹面积。时间推移分析表明，肽在膜变薄状态和孔状态之间可逆地转变，在这些状态之间转变的特征时间尺度上产生上限和下限（0.2< τ< 180 s）。
MelP5 is a lipophilic peptide with unique physical properties including the ability to create large and stable pores at low concentrations. Self-assembly into membrane spanning pores makes MelP5, systematically evolved from the primary toxic component of bee venom, a promising candidate for future applications in the pharmaceutical arena, as it offers a robust mechanism of drug delivery. Despite significant importance, little is known about the mechanism by which MelP5 remodels the lipid bilayer upon binding. Here, we demonstrate by atomic force microscope imaging that MelP5 interacts with a lipid bilayer in one of two ways: surface bound, which causes a thinning of the bilayer, or insertion into the membrane, which creates pores. Thinning of the bilayer was measured to be∼ 0.4 nm below the upper leaflet of the bilayer and was a prerequisite to pore formation. Pores exhibited many stable sizes, some of which were quite large. For example, approximately 20% of the pores exhibited footprint areas of 47+/-19.8 nm 2. Time lapse analysis demonstrated that the peptides transitioned reversibly between the membrane thinned state and pore state, yielding upper and lower bounds (0.2< τ< 180 s) on the characteristic time scale of transitions between these states.