蛋白转导域内在化机制的研究进展

Recent progress in internalization mechanism of protein transduction domain

蛋白转导域(protein transduction domain,PTD)可以携带外源生物大分子进入细胞,在分子生物学、细胞生物学的基础研究及生物技术应用中,都展示出良好的前景,应用广泛,但机制不甚明确。已知的PTD均有其关键的特定氨基酸存在和较强的正电荷分布,并具有独特的二级结构及空间构象,这些特殊的结构特征对其内在化机制起决定作用。目前认为巨胞饮作用是PTD入胞的主要机制, PTD在经过细胞表面糖胺聚糖紧密结合快速作用及电荷作用后,由脂筏蛋白介导的巨胞饮作用内在化,然后巨胞饮体脂质双层破裂,使蛋白转导域-大分子释放入胞浆及胞核。

Protein transduction domain （PTD） can carry a variety of large, biologically-active molecules into cells, and serves as a valuable biological tool in fundamental research and biotechnological applications. However, the mechanism of transduction remains elusive. Studies on the structure of PTD provide clues about the mechanism of PTD translocation. The specific amino acids with strong positive charge as well as the unique secondary structure and three dimensional conformation are all required for the translocation. These special structures play an important role in PTD internalization. At present, macropinocytosis is thought to be the major pathway of PTD internalization. PTD enters cells by rapid lipid rafts-mediated macropinocytosis after binding to the cell membrane via ionic interaction and the tight and rapid combination with glycosaminoglycans. The disruption of the macropinosome vesicle lipid bilayer ultimately results in the PTD -cargo release to the cytosol and nuclus.