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Peptides derived from the C-terminal domain of HIV-1 Viral Protein R in lipid bilayers: Structure, membrane positioning and gene delivery.
Biochimica et Biophysica Acta (BBA) - Biomembranes ( IF 2.8 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.bbamem.2019.183149
Arnaud Marquette 1 , Christian Leborgne 2 , Vanessa Schartner 3 , Evgeniy Salnikov 1 , Burkhard Bechinger 1 , Antoine Kichler 3
Affiliation  

Viral protein R (Vpr) is a small accessory protein of 96 amino acids that is present in Human and simian immunodeficiency viruses. Among the very different properties that Vpr possesses we can find cell penetrating capabilities. Based on this and on its capacity to interact with nucleic acids we previously investigated the DNA transfection properties of Vpr and subfragments thereof. We found that fragments of the C-terminal helical domain of Vpr are able to deliver efficiently plasmid DNA into different cell lines. As the amphipathic helix may play a role in the interactions with membranes, we investigated whether insertion of a proline residue in the α-helix modifies the transfection properties of Vpr. Unexpectedly, we found that the resulting Vpr55-82 Pro70 peptide was even more efficient than wild type Vpr55-82 in the gene delivery assays. Using circular dichroism, light scattering and solid-state NMR techniques, we characterized the secondary structure and interactions of Vpr and several mutants with model membranes. A model is proposed where the proline shifts the dissociation equilibrium of the peptide-cargo complex and thereby its endosomal release.

中文翻译:

脂双层中源自HIV-1病毒蛋白R C末端结构域的肽:结构,膜定位和基因传递。

病毒蛋白R(Vpr)是人和猿猴免疫缺陷病毒中存在的96个氨基酸的小辅助蛋白。在Vpr拥有的非常不同的特性中,我们可以发现细胞穿透能力。基于此及其与核酸相互作用的能力,我们先前研究了Vpr及其亚片段的DNA转染特性。我们发现,Vpr的C末端螺旋结构域的片段能够有效地将质粒DNA传递到不同的细胞系中。由于两亲性螺旋可能在与膜的相互作用中起作用,因此我们研究了脯氨酸残基在α-螺旋中的插入是否会改变Vpr的转染特性。出乎意料的是,我们发现,在基因递送测定中,所得的Vpr55-82 Pro70肽甚至比野生型Vpr55-82更有效。使用圆二色性,光散射和固态NMR技术,我们表征了Vpr和几个突变体与模型膜的二级结构和相互作用。提出了一种模型,其中脯氨酸改变了肽-货物复合物的解离平衡,从而改变了其内体释放。
更新日期:2019-12-07
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