Mahalingam S, Khan S A, Jabbar M A, Monken C E, Collman R G, Srinivasan A
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Virology. 1995 Feb 20;207(1):297-302. doi: 10.1006/viro.1995.1081.
Vpr is one of the auxiliary proteins encoded by the HIV-1 genome and is selectively incorporated into the virus particle. It has been shown that Vpr incorporation in the virus particle requires only the core protein Gag. In an effort to identify the domains of Vpr which are essential for incorporation into the HIV-1 virion, site-specific mutagenesis of vpr was carried out. Mutation of the highly conserved acidic residues in the N-terminal domain (amino acid positions 17-34) eliminated virion incorporation. These mutations disrupt a predicted amphipathic alpha-helical structure that is highly conserved among Vpr sequences. In contrast, alterations of the conserved cysteine (Cys76), basic domain (Arg87 and Lys95), and other residues (Gln65) did not impair the incorporation of Vpr into virus-like particles directed by HIV-1 Gag. The results presented here suggest that protein-protein interactions mediated through the putative helical domain of Vpr may participate in its incorporation into the virus particle.
Vpr是由HIV-1基因组编码的辅助蛋白之一，并被选择性地整合到病毒颗粒中。研究表明，Vpr整合到病毒颗粒中仅需要核心蛋白Gag。为了确定Vpr中对于整合到HIV-1病毒体至关重要的结构域，对vpr进行了位点特异性诱变。N端结构域（氨基酸位置17 - 34）中高度保守的酸性残基发生突变会消除病毒体整合。这些突变破坏了在Vpr序列中高度保守的预测两亲性α螺旋结构。相比之下，保守的半胱氨酸（Cys76）、碱性结构域（Arg87和Lys95）以及其他残基（Gln65）的改变并不损害Vpr整合到由HIV-1 Gag引导的病毒样颗粒中。此处呈现的结果表明，通过Vpr假定的螺旋结构域介导的蛋白质 - 蛋白质相互作用可能参与其整合到病毒颗粒中。
