CNRS-Université Montpellier, Centre d'études d'agents Pathogenes et de Biotechnologies pour la Santé, Montpellier, France.
CNRS-Université Grenoble, Institut National de Physique, Grenoble, France.
Sci Rep. 2016 Dec 23;6:39332. doi: 10.1038/srep39332.
The self-assembly of HIV-1 Gag polyprotein at the inner leaflet of the cell host plasma membrane is the key orchestrator of virus assembly. The binding between Gag and the plasma membrane is mediated by specific interaction of the Gag matrix domain and the PI(4,5)P lipid (PIP). It is unknown whether this interaction could lead to local reorganization of the plasma membrane lipids. In this study, using model membranes, we examined the ability of Gag to segregate specific lipids upon self-assembly. We show for the first time that Gag self-assembly is responsible for the formation of PIP lipid nanoclusters, enriched in cholesterol but not in sphingomyelin. We also show that Gag mainly partition into liquid-disordered domains of these lipid membranes. Our work strongly suggests that, instead of targeting pre-existing plasma membrane lipid domains, Gag is more prone to generate PIP/Cholesterol lipid nanodomains at the inner leaflet of the plasma membrane during early events of virus assembly.
HIV-1 Gag 多聚蛋白在内质网宿主质膜内层的自组装是病毒组装的关键协调者。Gag 与质膜的结合是由 Gag 基质域和 PI(4,5)P 脂质（PIP）的特异性相互作用介导的。目前尚不清楚这种相互作用是否会导致质膜脂质的局部重排。在这项研究中，我们使用模型膜研究了 Gag 在自组装时分离特定脂质的能力。我们首次表明，Gag 自组装负责形成富含胆固醇但不含鞘磷脂的 PIP 脂质纳米簇。我们还表明，Gag 主要分配到这些脂质膜的液体无序域。我们的工作强烈表明，Gag 在病毒组装的早期事件中更倾向于在质膜内层生成 PIP/胆固醇脂质纳米区，而不是靶向预先存在的质膜脂质区。
