Distinct domains in herpes simplex virus type 1 US11 protein mediate post-transcriptional transactivation of human T-lymphotropic virus type I envelope glycoprotein gene expression and specific binding to the Rex responsive element
Distinct domains in herpes simplex virus type 1 US11 protein mediate post-transcriptional transactivation of human T-lymphotropic virus type I envelope glycoprotein gene expression and specific binding to the Rex responsive element
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DOI：
10.1099/0022-1317-79-7-1593
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发表时间：
1998-07-01
影响因子：
3.8
通讯作者：
Diaz, JJ
中科院分区：
文献类型：
--
作者：
Schaerer-Uthurralt, N;Erard, M;Diaz, JJ
单纯疱疹病毒I型(HSV-1)US11蛋白是一种RNA结合蛋白，通过与位于env基因3‘端的Rex反应元件(XRE)相互作用，能够介导人T淋巴细胞I型嗜T细胞病毒(HTLV-I)囊膜糖蛋白基因的转录后反式激活，鉴于这一功能活性，并且由于US11蛋白能够替代HTLV-I型Rex蛋白，因此假设US11蛋白至少具有两个功能结构域，一个用于与靶RNA特异性相互作用的RNA结合域，以及参与该mRNA运输和翻译的效应结构域。重组的US11野生型和缺失蛋白分别与XRE和HSV-1UL34 RNA(US11蛋白的天然靶标)结合和反式激活HTLV-I env基因表达。US11蛋白的C-末端部分由20-24个XPR重复序列组成，是介导RNA结合的必要条件和充分条件，结构预测分析表明该结构域的构象可能是多脯氨酸II型螺旋，定位在US11蛋白N-末端区域的前40个氨基酸中是效应域，该基因的缺失产生了US11(Delta 1-40)，一个反式显性负突变，这些结果表明US11蛋白与Rex和Rev等蛋白的结构不同，尽管它们的功能相似。
Herpes simplex virus type 1 (HSV-1) US 1 1 protein is an RNA-binding protein which is able to mediate post-transcriptional transactivation of human T-lymphotropic virus type I (HTLV-I) envelope glycoprotein gene expression by interacting with the Rex responsive element (XRE) located at the 3' end of the env mRNA, In view of this functional activity, and because US 1 1 protein is capable of substituting for HTLV-I Rex protein, it was hypothesized that US11 protein should exhibit at least two functional domains, an RNA-binding domain for specific interaction with the target RNA, and an effector domain involved in transport and translation of this mRNA, Recombinant US11 wild-type and deleted proteins were tested for their ability (i) to bind to the XRE and to HSV-1 UL34 RNA, the natural target of US11 protein, and (ii) to transactivate HTLV-I env gene expression, The C-terminal half of US11 protein, consisting of 20-24 XPR repeats, was necessary and sufficient to mediate RNA-binding with a high affinity and specificity, Structure prediction analyses showed the likely conformation of this domain to be that of a polyproline type II helix, Localized within the first 40 amino acids of the N-terminal region of US11 protein was the effector domain, deletion of which created US11(Delta 1-40), a trans-dominant negative mutant, These results demonstrate structural differences between US11 protein and proteins like Rex and Rev, despite their functional similarities.