Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex
Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex
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DOI：
10.1074/jbc.273.21.13347
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发表时间：
1998-05-22
影响因子：
4.8
通讯作者：
Bukrinsky, M
中科院分区：
文献类型：
--
作者：
Popov, S;Rexach, M;Bukrinsky, M
人类免疫缺陷病毒1型（HIV-1）在非分裂细胞中的复制关键取决于病毒前整合复合物进入细胞核。最近的证据表明，病毒蛋白R（Vpr）在这一过程中起着关键的调节作用，通过结合细胞核定位信号的细胞受体，并增加其对核定位信号的亲和力。体外结合试验用于研究Vpr在HIV-1整合前复合物（PIC）与核孔复合物对接中的作用。缺乏Vpr的突变型HIV-1 PIC与分离的细胞核和重组核孔蛋白对接的能力受损。虽然Vpr本身与核孔蛋白相关，但Vpr（+）PIC的对接依赖于核转运蛋白β，并被β抗体阻断。Vpr通过阻止核孔蛋白刺激的输入复合物解离来稳定对接。这些结果表明，Vpr功能的运输HIV-1基因组的核孔复合物的生化机制。
Replication of human immunodeficiency virus type 1 (HIV-1) in non-dividing cells depends critically on import of the viral preintegration complex into the nucleus. Recent evidence suggests that viral protein R (Vpr) plays a key regulatory role in this process by binding to karyopherin alpha, a cellular receptor for nuclear localization signals, and increasing its affinity for the nuclear localization signals. An in vitro binding assay was used to investigate the role of Vpr in docking of the HIV-1 preintegration complex (PIC) to the nuclear pore complex. Mutant HIV-1 PICs that lack Vpr were impaired in the ability to dock to isolated nuclei and recombinant nucleoporins. Although Vpr by itself associated with nucleoporins, the docking of Vpr(+) PICs was dependent on karyopherin beta and was blocked by antibodies to beta. Vpr stabilized docking by preventing nucleoporin-stimulated dissociation of the import complex. These results suggest a biochemical mechanism for Vpr function in transport of the HIV-1 genome across the nuclear pore complex.