NMR structure of the HIV-1 regulatory protein VPR
NMR structure of the HIV-1 regulatory protein VPR
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DOI：
10.1016/s0022-2836(03)00060-3
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发表时间：
2003-03-14
影响因子：
5.6
通讯作者：
Roques, BP
中科院分区：
文献类型：
--
作者：
Morellet, N;Bouaziz, S;Roques, BP
人类免疫缺陷病毒1型（HIV-1）基因组编码高度保守的调控基因产物Vpr(96个残基，14 kDa)，该基因被整合到病毒粒子中。在感染细胞中，Vpr在病毒周期后期表达，被认为在HIV-1复制的早期阶段发挥作用，如前整合复合体的核迁移、前病毒基因组的转录、G2期阻断细胞的病毒增殖和细胞凋亡现象的调控。Vpr通过诱导单核细胞和巨噬细胞等非分裂细胞的感染，在长期的艾滋病疾病中起着关键作用。为了深入了解Vpr的结构-功能关系，我们用22个标记的氨基酸合成了（1-96）Vpr蛋白。在CD3CN存在下和在低pH纯水中分析了其三维结构，并通过约束模拟退火进行了细化。该蛋白的结构特征是三个定义明确的α -螺旋：17-33、38-50和56-77，它们被灵活的N和c端结构域包围。与TFE存在时得到的结构相反，三个a-螺旋围绕由Leu、Ile、Val和芳香残基组成的疏水核心折叠，这一点可以通过大量的远程NOES来证明。这种结构解释了Vpr与不同靶标的相互作用。2003爱思唯尔科学有限公司版权所有。
The human immunodeficiency virus type 1 (HIV-1) genome encodes a highly conserved regulatory gene product, Vpr (96 residues, 14 kDa), which is incorporated into virions. In the infected cells, Vpr, expressed late in the virus cycle, is believed to function in the early phases of HIV-1 replication, such as nuclear migration of pre-integration complex, transcription of the proviral genome, viral multiplication by blocking cells in G2 phase and regulation of apoptosis phenomenon. Vpr has a critical role in long term AIDS disease by inducing infection in non-dividing cells such as monocytes and macrophages. To gain insight into the structure-function relationships of Vpr, the (1-96)Vpr protein was synthesized with 22 labeled amino acids. Its 3D structure was analyzed in the presence of CD3CN and in pure water at low pH and refined by restrained simulated annealing. The structure of the protein is characterized by three well-defined alpha-helices: 17-33, 38-50 and 56-77 surrounded by flexible N and C-terminal domains. In contrast to the structure obtained in the presence of TFE, the three a-helices are folded around a hydrophobic core constituted of Leu, Ile, Val and aromatic residues as illustrated by numerous long range NOES. This structure accounts for the interaction of Vpr with different targets. (C) 2003 Elsevier Science Ltd. All rights reserved.