Functional interaction of human immunodeficiency virus type 1 Vpu and Gag with a novel member of the tetratricopeptide repeat protein family

Functional interaction of human immunodeficiency virus type 1 Vpu and Gag with a novel member of the tetratricopeptide repeat protein family
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DOI:
10.1128/jvi.72.6.5189-5197.1998
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发表时间:
1998-06-01
影响因子:
5.4
通讯作者:
Panganiban, AT
Panganiban, AT
中科院分区:
医学2区
文献类型:
--
作者:
Callahan, MA;Handley, MA;Panganiban, AT

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病毒蛋白 U (Vpu) 是由 1 型人类免疫缺陷病毒 (HIV-1) 编码的蛋白质,可促进病毒受体 CD4 的降解,并增强细胞中病毒颗粒的释放。我们分离了一种 cDNA,它编码一种新型细胞蛋白,该蛋白在体外、体内和酵母细胞中与 Vpu 相互作用。这种 Vpu 结合蛋白 (UBP) 的分子量为 41 kDa,在人体组织中以 RNA 水平广泛表达。 UBP 是四肽重复 (TPR) 蛋白家族的新成员,包含 4 个 34 个氨基酸 TPR 基序的拷贝。其他含有 TPR 基序的蛋白质包括亲免素超家族的成员、细胞器靶向蛋白和蛋白磷酸酶。 UBP 还直接与 HN-I Gag 蛋白(病毒衣壳的主要结构成分)相互作用。然而,当 Vpu 和 Gag 共表达时,UBP 和 Gag 之间的稳定相互作用就会减弱。此外,UBP 在病毒产生细胞中的过度表达导致 HIV-1 病毒颗粒释放显着减少。总而言之,这些数据表明 UBP 在 Vpu 介导的颗粒释放增强中发挥作用。
Viral protein U (Vpu) is a protein encoded by human immunodeficiency virus type 1 (HIV-1) that promotes the degradation of the virus receptor, CD4, and enhances the release of virus particles from cells. We isolated a cDNA that encodes a novel cellular protein that interacts with Vpu in vitro, in vivo, and in yeast cells. This Vpu-binding protein (UBP) has a molecular mass of 41 kDa and is expressed ubiquitously in human tissues at the RNA level. UBP is a novel member of the tetratricopeptide repeat (TPR) protein family containing four copies of the 34-amino-acid TPR motif. Other proteins that contain TPR motifs include members of the immunophilin superfamily, organelle-targeting proteins, and a protein phosphatase. UBP also interacts directly with HN-I Gag protein, the principal structural component of the viral capsid, However, when Vpu and Gag are coexpressed, stable interaction between UBP and Gag is diminished. Furthermore, overexpression of UBP in virus-producing cells resulted in a significant reduction in HIV-1 virion release. Taken together, these data indicate that UBP plays a role in Vpu-mediated enhancement of particle release.