Lipid-specific interactions determine the organization and dynamics of membrane-active peptide melittin.
Lipid-specific interactions determine the organization and dynamics of membrane-active peptide melittin.
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脂质特异性相互作用决定膜活性肽蜂毒肽的组织和动力学
DOI：
10.1039/d0sm00046a
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发表时间：
2020-03
期刊：
影响因子：
3.4
通讯作者：
Yang Kai
中科院分区：
文献类型：
--
作者：
Deng Zhixiong;Lu Xuemei;Xu Cheng;Yuan Bing;Yang Kai
不同细胞的细胞膜在脂类成分上有很大差异，因此提供了不同的生物环境来调节生物大分子的扩散、组织和最终的功能。然而，具体的调控机制仍然不清楚，特别是考虑到目前过度使用简化的膜模型，如纯卵磷脂(PC)膜。在这项工作中，我们以典型的膜活性多肽蜂毒素为例，通过将分子动力学模拟作为计算显微镜，证明了更复杂的膜环境，如细菌(IME)或质膜(PM)，将显著改变蜂毒素的组织和动力学。研究发现，在这些膜系统中，由于肽的组装状态不同，加入蜂毒素会不同程度地减少脂类的侧向扩散。在纯PC膜中，蜂毒素倾向于以四聚体或三聚体的形式聚集，而在IME或PM膜中，其齐聚程度明显降低。更令人惊讶的是，蜂毒素与神经节苷脂GM3在PM中表现出很强的亲和力，导致蜂毒素-GM3纳米团簇的形成，阻碍了它的扩散和进一步的齐聚。此外，蜂毒素残基序列的微小变化可以调节多肽低聚体的程度或结构。我们的工作为研究特定膜环境中造孔肽的组织和动力学提供了一个典型的例子，对膜中多肽序列的优化和螺旋束的设计具有重要的意义。
The cell membranes of different cells deviate significantly in lipid compositions and thus provide varying biological environments to modulate the diffusion, organization and the resultant function of biomacromolecules. However, the detailed modulation mechanism remains elusive especially in consideration of the current overuse of the simplified membrane models such as the pure phosphatidylcholine (PC) membrane. In this work, with the typical membrane-active peptide melittin, we demonstrated that a more complicated membrane environment, such as the bacterial (IME) or plasma membrane (PM), would significantly change the organization and dynamics of melittin, by using molecular dynamics simulations as a "computational microscope". It was found that in these membrane systems, adding melittin would cause a varying degree of reduction in the lateral diffusion of lipids due to the different assembly states of peptides. Melittin tended to aggregate to oligomers in the pure PC membrane, mostly as a tetramer or trimer, while in IME or PM, its degree of oligomerization was significantly reduced. More surprisingly, melittin displayed a strong affinity with ganglioside GM3 in PM, leading to the formation of melittin-GM3 nanoclusters, which hindered its diffusion and further oligomerization. Additionally, small changes in the residue sequence of melittin could modulate the degree or structure of the peptide oligomer. Our work provides a typical example of a study on the organization and dynamics of pore-forming peptides in specific membrane environments and has great significance on the optimization of peptide sequences and the design of helix bundles in the membrane for target biological function.
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影响因子：
2
作者：
R. Dmochowski
通讯作者：
R. Dmochowski
DOI：
10.1016/j.respe.2020.09.004
发表时间：
2020-10-10
期刊：
Revue D'Epidemiologie et De Sante Publique
影响因子：
--
作者：
La rédaction
通讯作者：
La rédaction
影响因子：
9.3
作者：
通讯作者：
--
影响因子：
5.9
作者：
Craighead FL
通讯作者：
Craighead FL