HIV-1 matrix-31 membrane binding peptide interacts differently with membranes containing PS vs. PI(4,5)P(2).

HIV-1 matrix-31 membrane binding peptide interacts differently with membranes containing PS vs. PI(4,5)P(2).
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DOI:
10.1016/j.bbamem.2016.09.010
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发表时间:
2016-12
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Tristram-Nagle S
Tristram-Nagle S
中科院分区:
其他
文献类型:
--
作者:
O'Neil L;Andenoro K;Pagano I;Carroll L;Langer L;Dell Z;Perera D;Treece BW;Heinrich F;Lösche M;Nagle JF;Tristram-Nagle S

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HIV-1在T细胞质膜(PM)上的有效组装特别需要PI(4,5)P2。先前表明,Gag前体多聚蛋白Pr 55 Gag上的基质蛋白(MA)的高碱性区域(HBR)是膜缔合所需的。MA是N-末端肉豆蔻酰化的,这增强了其对膜的亲和力。在这项工作中,我们使用X-射线散射和中子反射率来确定如何的物理性质和结构的脂质双层响应于添加结合域肽,无论是在肉豆蔻酰化的形式(MA 31 myr)或没有肉豆蔻酰基(MA 31)。中子反射率测量表明,肽主要位于烃类内部。扩散X-射线散射显示膜特性的差异后,添加肽和方向的变化取决于脂质组合物。PI(4,5)P2-含有双层软化,变薄,并成为较不有序的肽浓度增加。与此相反,含有POPS的双层膜具有相等的净电荷,首先硬化,增厚,并变得更加有序的肽浓度的增加。由于在与蛋白质接触时软化宿主细胞的PM降低了膜重构的自由能,从而潜在地促进病毒颗粒的出芽,我们的结果表明PI(4,5)P2在病毒组装中的作用超出了特异性立体化学膜结合。这些研究加强了脂质在病毒学中的重要性。
Efficient assembly of HIV-1 at the plasma membrane (PM) of the T-cell specifically requires PI(4,5)P2. It was previously shown that a highly basic region (HBR) of the matrix protein (MA) on the Gag precursor polyprotein Pr55Gag is required for membrane association. MA is N-terminally myristoylated, which enhances its affinity to membranes. In this work we used X-ray scattering and neutron reflectivity to determine how the physical properties and structure of lipid bilayers respond to the addition of binding domain peptides, either in the myristoylated form (MA31myr) or without the myristoyl group (MA31). Neutron reflectivity measurements showed the peptides predominantly located in the hydrocarbon interior. Diffuse X-ray scattering showed differences in membrane properties upon addition of peptides and the direction of the changes depended on lipid composition. The PI(4,5)P2-containing bilayers softened, thinned and became less ordered as peptide concentration increased. In contrast, POPS-containing bilayers with equivalent net charge first stiffened, thickened and became more ordered with increasing peptide concentration. As softening the host cell’s PM upon contact with the protein lowers the free energy for membrane restructuring, thereby potentially facilitating budding of viral particles, our results suggest that the role of PI(4,5)P2 in viral assembly goes beyond specific stereochemical membrane binding. These studies reinforce the importance of lipids in virology.
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