Arginine-rich peptides - An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery
Arginine-rich peptides - An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery
复制标题
DOI：
10.1074/jbc.m007540200
复制
发表时间：
2001-02-23
影响因子：
4.8
通讯作者：
Sugiura, Y
中科院分区：
文献类型：
--
作者：
Futaki, S;Suzuki, T;Sugiura, Y
据报道，来源于人免疫缺陷病毒（HIV）-1达特蛋白（位置48-60）的碱性肽具有穿过细胞膜移位并在细胞核中积累的能力，其特征用于将外源蛋白递送到细胞中。基于对小鼠巨噬细胞RAW 264.7细胞的荧光显微镜观察，我们发现多种富含精氨酸的肽具有与达特-（48-60）非常相似的易位活性。这些肽包括如（D）-氨基酸-和亮氨酸-取代的达特-（48-60）、源自病毒蛋白如HIV-1 Rev和鸡舍病毒外壳蛋白的RNA结合肽、亮氨酸拉链蛋白如癌症相关蛋白c-Fos和c-Jun的DNA结合片段、以及酵母转录因子GCN 4，这些片段没有共同的特定一级和二级结构，除了它们在序列中有几个精氨酸残基。此外，这些肽甚至能够在4 ℃下被内化。这些结果强烈地表明，可能存在一种普遍存在于富含精氨酸的肽中的共同内化机制，这不能用典型的内吞作用来解释。（n = 4-16）肽，我们还证明了对于有效的易位，存在最佳的精氨酸残基数目（n类似于8）。
A basic peptide derived from human immunodeficiency virus (HIV)-1 Tat protein (positions 48-60) has been reported to have the ability to translocate through the cell membranes and accumulate in the nucleus, the characteristics of which are utilized for the delivery of exogenous proteins into cells. Based on the fluorescence microscopic observations of mouse macrophage RAW264.7 cells, we found that various arginine-rich peptides have a translocation activity very similar to Tat-(48-60). These included such peptides as the (D)-amino acid- and arginine-substituted Tat-(48-60), the RNA-binding peptides derived from virus proteins, such as HIV-1 Rev, and flock house virus coat proteins, and the DNA binding segments of leucine zipper proteins, such as cancer-related proteins c-Fos and c-Jun, and the yeast transcription factor GCN4, These segments have no specific primary and secondary structures in common except that they have several arginine residues in the sequences. Moreover, these peptides were able to be internalized even at 4 degreesC, These results strongly suggested the possible existence of a common internalization mechanism ubiquitous to arginine-rich peptides, which is not explained by a typical endocytosis, Using (Arg)(n) (n = 4-16) peptides, we also demonstrated that there would be an optimal number of arginine residues (n similar to 8) for the efficient translocation.