Binding modes of protegrin-1, a beta-strand antimicrobial peptide, in lipid bilayers
Binding modes of protegrin-1, a beta-strand antimicrobial peptide, in lipid bilayers
复制标题
DOI：
10.1080/08927020701313737
复制
发表时间：
2007-01-01
影响因子：
2.1
通讯作者：
Larson, R. G.
中科院分区：
文献类型：
--
作者：
Kandasamy, S. K.;Larson, R. G.
分子动力学(MD)模拟结果表明，在不同疏水宽度的模型脂双分子膜上，抗菌素-1至少有两种不同的结合模式。在其中一种模式中，三个阳离子精氨酸残基与一个双层小叶结合，另外三个精氨酸残基与相反的小叶结合，而在第二种结合模式中，四个精氨酸与一个小叶结合，两个与另一小叶结合。N-末端区域前四个残基的高构象灵活性促进了多种结合模式的存在，其序列为RGGR。其中一种结合模式比另一种模式引起更大的双层破坏，并且在任何一种模式下，对于双分子层宽度较小的脂膜，双层破坏都较小。在PG-1多肽存在下，对初始随机的脂质/水混合物的自组装模拟表明，该体系演化成一个双层，在两个脂质小叶上有一个稳定的水孔。脂头基团和PG-1肽稳定水孔。
Molecular dynamics ( MD) simulations of the interactions of a beta-strand antimicrobial peptide, protegrin-1, with model lipid bilayers of different hydrophobic widths show that protegrin-1 possesses at least two distinct binding modes in the transmembrane orientation. In one of the modes, three of the cationic arginine residues bind to one bilayer leaflet and the other three arginine residues bind to the opposite leaflet, while in the second binding mode, four arginines bind to one leaflet and two to the other. The existence of multiple binding modes is facilitated by the high conformational flexibility of the first four residues of the N-terminal region, with a sequence of RGGR. One of the binding modes causes a larger bilayer disruption than the other, and in either mode, the bilayer disruption is smaller for lipid membranes with smaller bilayer widths. Simulations of the self-assembly of initially random lipid/water mixtures in the presence of PG-1 peptides show that the system evolves into a bilayer, with a stable water pore spanning the two lipid leaflets. Lipid head groups and the PG-1 peptide stabilize the water pore.