Three-dimensional structure of HIV-1VIF constructed by comparative modeling and the function characterization analyzed by molecular dynamics simulation
Three-dimensional structure of HIV-1VIF constructed by comparative modeling and the function characterization analyzed by molecular dynamics simulation
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DOI：
10.1039/b612050d
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Zhang, Lihe
中科院分区：
文献类型：
--
作者：
Lv, Wei;Liu, Zhenming;Zhang, Lihe
VIF是HIV-1的六个辅助蛋白之一。它已被证明是HIV-1在人体内存活和保持病毒传染性所必需的。人们强烈期望通过阻断VIF的生物学途径来实现一种新的治疗HIV-1感染的策略。本文基于VHL和NarL两个模板，分别构建了VIF的c端结构域和n端结构域，通过对比建模，构建了VIF的三维模型。建立了VIF-ElonginB-ElonginC配合物的分子动力学模型，研究了VIF与ElonginB-ElonginC的相互作用。利用诱变技术鉴定了假定的SOCS-box中一些保守残基的功能。结果表明，关键残基的突变导致VIF与ElonginB-ElonginC之间的相互作用中断，与实验观察结果一致。因此，这些新的VIF及其复合物模型为在分子水平上研究VIF的功能提供了结构信息。
VIF is one of the six accessory proteins of HIV-1. It has been shown to be necessary for the survival of HIV-1 in the human body and for the retention of viral infectivity. It is strongly expected that a new therapeutic strategy against HIV-1 infection could be realized by blocking the biological pathway to VIF. In this paper, a three-dimensional model of VIF was constructed by comparative modeling based on two templates, VHL and NarL, which were used to construct the C-terminal domain and N-terminal domain of VIF, respectively. A model of the VIF-ElonginB-ElonginC complex was constructed, and molecular dynamics simulations were used to investigate the interactions between VIF and ElonginB-ElonginC. Mutagenesis was used to identify the function of some conserved residues in the putative SOCS-box. The results showed that the mutations of the critical residues led to the disruption of the interactions between VIF and ElonginB-ElonginC, consistent with experimental observations. These novel models of VIF and its complex has therefore provided structural information for investigating the function of VIF at the molecular level.