Role of the HIV-1 Matrix Protein in Gag Intracellular Trafficking and Targeting to the Plasma Membrane for Virus Assembly.
Role of the HIV-1 Matrix Protein in Gag Intracellular Trafficking and Targeting to the Plasma Membrane for Virus Assembly.
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DOI：
10.3389/fmicb.2012.00055
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发表时间：
2012
影响因子：
5.2
通讯作者：
Saad JS
中科院分区：
文献类型：
--
作者：
Ghanam RH;Samal AB;Fernandez TF;Saad JS
人类免疫缺陷病毒1型（HIV-1）编码一种称为Gag的多肽，该多肽能够在不存在任何细胞或病毒成分的情况下在体外形成病毒样颗粒。在HIV-1感染的晚期，Gag多聚蛋白被转运到质膜（PM）进行组装。在过去的二十年中，体内、体外和结构研究表明，Gag运输和靶向PM是精心策划的事件，其依赖于多种因素，包括细胞蛋白和特异性膜脂质。Gag的基质（MA）结构域一直是这些研究的焦点，因为它似乎参与了多种细胞内相互作用，这些相互作用被认为对病毒组装和复制至关重要。Gag和PM之间的互动可能是最容易理解的。现已确定，Gag在PM上点状位点上的最终定位是由Gag的MA结构域与磷脂酰肌醇-4，5-二磷酸[PI（4，5）P2]（一种位于PM内小叶上的次要脂质）之间的特异性相互作用介导的。基于结构的研究表明，PI（4，5）P2与MA的结合诱导微小的构象变化，导致肉豆蔻基（myr）基团的暴露。暴露的MYR组也引发钙调蛋白的结合，增强的因素，促进蛋白质自协会一样的衣壳结构域的加格，并调制pH值。尽管在定义病毒和细胞的逆转录病毒的组装和释放的决定因素的稳步进展，加格的细胞内相互作用和贩运到其组装位点在感染的细胞知之甚少。在这篇综述中，我们总结了目前的理解MA在HIV复制的结构和功能的作用。
Human immunodeficiency virus type-1 (HIV-1) encodes a polypeptide called Gag that is able to form virus-like particles in vitro in the absence of any cellular or viral constituents. During the late phase of the HIV-1 infection, Gag polyproteins are transported to the plasma membrane (PM) for assembly. In the past two decades, in vivo, in vitro, and structural studies have shown that Gag trafficking and targeting to the PM are orchestrated events that are dependent on multiple factors including cellular proteins and specific membrane lipids. The matrix (MA) domain of Gag has been the focus of these studies as it appears to be engaged in multiple intracellular interactions that are suggested to be critical for virus assembly and replication. The interaction between Gag and the PM is perhaps the most understood. It is now established that the ultimate localization of Gag on punctate sites on the PM is mediated by specific interactions between the MA domain of Gag and phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], a minor lipid localized on the inner leaflet of the PM. Structure-based studies revealed that binding of PI(4,5)P2 to MA induces minor conformational changes, leading to exposure of the myristyl (myr) group. Exposure of the myr group is also triggered by binding of calmodulin, enhanced by factors that promote protein self-association like the capsid domain of Gag, and is modulated by pH. Despite the steady progress in defining both the viral and cellular determinants of retroviral assembly and release, Gag’s intracellular interactions and trafficking to its assembly sites in the infected cell are poorly understood. In this review, we summarize the current understanding of the structural and functional role of MA in HIV replication.
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影响因子：
3.3
作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.191224698
发表时间：
2001-09-11
影响因子：
11.1
作者：
Campbell, S;Fisher, RJ;Rein, A
通讯作者：
Rein, A