Structural model of the Rev regulatory protein from equine infectious anemia virus.
Structural model of the Rev regulatory protein from equine infectious anemia virus.
复制标题
DOI：
10.1371/journal.pone.0004178
复制
发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Dobbs, Drena
中科院分区：
文献类型：
--
作者：
Ihm, Yungok;Sparks, Wendy O.;Lee, Jae-Hyung;Cao, Haibo;Carpenter, Susan;Wang, Cai-Zhuang;Ho, Kai-Ming;Dobbs, Drena
Rev是马传染性贫血病毒（EIAV）和其他慢病毒（包括HIV-1）中的重要调节蛋白。它结合不完全剪接的病毒mRNA，并将它们从细胞核运送到细胞质，这是产生病毒结构蛋白和基因组RNA的关键先决条件。尽管Rev在感染性病毒的产生中起重要作用，但由于缺乏实验确定的全长蛋白质结构，针对Rev的抗病毒疗法的开发受到阻碍。我们已经使用了一个计算和生物化学相结合的方法来生成和评估的Rev蛋白的结构模型。模型EIAV Rev（ERev）结构包括总共6个螺旋，其中4个形成反平行四螺旋束。第一个螺旋含有富含亮氨酸的核输出信号（内斯）。富含精氨酸的RNA结合基序RRDRW位于溶剂暴露的环区。预测Rev活性所需的ERLE基序被埋在模型结构的核心中，在那里它在Rev折叠的稳定中起着至关重要的作用。该结构模型得到现有遗传和功能数据以及预测对整体结构完整性至关重要的残基的靶向诱变的支持。我们预测的结构应该增加对Rev结构-功能关系的理解，并可能为慢病毒疾病新疗法的设计提供基础。
Rev is an essential regulatory protein in the equine infectious anemia virus (EIAV) and other lentiviruses, including HIV-1. It binds incompletely spliced viral mRNAs and shuttles them from the nucleus to the cytoplasm, a critical prerequisite for the production of viral structural proteins and genomic RNA. Despite its important role in production of infectious virus, the development of antiviral therapies directed against Rev has been hampered by the lack of an experimentally-determined structure of the full length protein. We have used a combined computational and biochemical approach to generate and evaluate a structural model of the Rev protein. The modeled EIAV Rev (ERev) structure includes a total of 6 helices, four of which form an anti-parallel four-helix bundle. The first helix contains the leucine-rich nuclear export signal (NES). An arginine-rich RNA binding motif, RRDRW, is located in a solvent-exposed loop region. An ERLE motif required for Rev activity is predicted to be buried in the core of modeled structure where it plays an essential role in stabilization of the Rev fold. This structural model is supported by existing genetic and functional data as well as by targeted mutagenesis of residues predicted to be essential for overall structural integrity. Our predicted structure should increase understanding of structure-function relationships in Rev and may provide a basis for the design of new therapies for lentiviral diseases.
登录
查看更多内容
DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
影响因子：
--
作者：
Holm, Liisa;Kaariainen, Sakari;Plewczynski, Dariusz
通讯作者：
Plewczynski, Dariusz
影响因子：
3.7
作者：
Belshan, M;Baccam, P;Carpenter, S
通讯作者：
Carpenter, S
影响因子：
5.4
作者：
Lee, JH;Murphy, SC;Carpenter, S
通讯作者：
Carpenter, S
DOI：
10.1073/pnas.88.12.5317
发表时间：
1991-06-01
影响因子：
11.1
作者：
LYU, PC;SHERMAN, JC;KALLENBACH, NR
通讯作者：
KALLENBACH, NR