Structural and molecular determinants of HIV-1 Gag binding to the plasma membrane.
Structural and molecular determinants of HIV-1 Gag binding to the plasma membrane.
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DOI：
10.3389/fmicb.2015.00232
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发表时间：
2015
影响因子：
5.2
通讯作者：
Saad JS
中科院分区：
文献类型：
--
作者：
Vlach J;Saad JS
Gag 多蛋白靶向质膜 (PM) 进行组装是 1 型免疫缺陷病毒 (HIV-1) 感染后期的关键事件。 Gag 与 PM 的结合是通过肉豆蔻酰化基质 (MA) 结构域和 PM 脂质之间的相互作用介导的。尽管过去二十年对 Gag 和 MA 与膜结合进行了广泛的生化和体外研究，但磷脂酰肌醇-4,5-二磷酸 [PI(4,5)P2] 在 Gag 与 PM 结合中的作用的发现引发了一系列旨在阐明逆转录病毒 Gag-PM 结合分子机制的研究。长期以来，MA 高度保守的碱性区域和酸性磷脂之间的静电相互作用一直被认为是 Gag-膜相互作用的主要驱动力。然而，最近的研究表明，该机制相当复杂，因为其他因素（例如以酰基链和胆固醇为代表的膜内部的疏水性）也发挥着重要作用。在这里，我们总结了目前对 HIV-1 Gag-膜相互作用在分子和结构水平上的理解，并简要讨论了控制其他逆转录病毒 MA 蛋白与 PM 相互作用的潜在力量。
Targeting of the Gag polyprotein to the plasma membrane (PM) for assembly is a critical event in the late phase of immunodeficiency virus type-1 (HIV-1) infection. Gag binding to the PM is mediated by interactions between the myristoylated matrix (MA) domain and PM lipids. Despite the extensive biochemical and in vitro studies of Gag and MA binding to membranes over the last two decades, the discovery of the role of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] in Gag binding to the PM has sparked a string of studies aimed at elucidating the molecular mechanism of retroviral Gag–PM binding. Electrostatic interactions between a highly conserved basic region of MA and acidic phospholipids have long been thought to be the main driving force for Gag–membrane interactions. However, recent studies suggest that the mechanism is rather complex since other factors such as the hydrophobicity of the membrane interior represented by the acyl chains and cholesterol also play important roles. Here we summarize the current understanding of HIV-1 Gag–membrane interactions at the molecular and structural levels and briefly discuss the underlying forces governing interactions of other retroviral MA proteins with the PM.