Mapping of herpes simplex virus-1 VP22 functional domains for inter- and subcellular protein targeting
Mapping of herpes simplex virus-1 VP22 functional domains for inter- and subcellular protein targeting
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DOI：
10.1038/sj.gt.3301493
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发表时间：
2001-07-01
期刊：
影响因子：
5.1
通讯作者：
Dilber, MS
中科院分区：
文献类型：
--
作者：
Aints, A;Güven, H;Dilber, MS
单纯疱疹病毒1型(HSV-1)被膜蛋白VP22已被用作运输蛋白的载体。它具有离开产生它的细胞并进入邻近细胞的显著特性，这种特性已被用于运送治疗性蛋白、P53和单纯疱疹病毒胸苷激酶(Tk)。它有一个复杂的表达模式和亚细胞定位。VP22的功能包括细胞间转运、与微丝的结合和捆绑、诱导细胞骨架崩溃、有丝分裂过程中的核转位以及与染色质和核膜的结合。VP22包含这些功能中的每一个的区域尚未表征。发现具有胞间扩散特性的区域将有助于运输功能的增强。通过构建绿色荧光蛋白(GFP)标记的VP22的一系列缺失结构，我们已经将VP22的功能定位到多肽的特定区域如下：细胞间转运AA 81-195，细胞骨架结合和重组-AA 159-267；核靶向，抑制细胞骨架崩溃-AA 81-121；以及核靶向和促进细胞间转运-AA 267-301。VP22功能的分离使人们能够重点研究VP22介导的转运机制，提高VP22的转运效率。
The herpes simplex virus 1 (HSV-1) tegument protein VP22 has been utilised as a vehicle for trafficking proteins. It has a remarkable property of exiting the cell that is producing it and entering the neighbouring cells, which has been used to deliver therapeutic proteins, p53 and herpes simplex virus thymidine kinase (tk). It has a complex pattern of expression and subcellular localisation. Functions of VP22 include intercellular transport, binding to and bundling of microfilaments, inducing cytoskeleton collapse, nuclear translocation during mitosis, and binding to chromatin and nuclear membrane. The regions of VP22 which contain each of these functions have not been characterised. Finding the region carrying the property of intercellular spread would facilitate enhancement of transport function. By constructing a series of deletion constructs of VP22 tagged by the green fluorescent protein (GFP) we have mapped the functions of VP22 to specific regions in the polypeptide as follows: intercellular transport aa 81-195, binding and reorganisation of cytoskeleton - aa 159-267; nuclear targeting, inhibition of cytoskeleton collapse - aa 81-121; and nuclear targeting and facilitation of intercellular transport - aa 267-301. Separation of VP22 functions enables focus on the mechanism of VP22-mediated transport and improve the transportation efficiency of VP22.