Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 02841, Korea.
Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
Int J Mol Sci. 2020 Jan 30;21(3):897. doi: 10.3390/ijms21030897.
Hepatitis C virus (HCV) p7 is known to be a nonselective cation channel for HCV maturation. Because the interaction of HCV proteins with host lipids in the endoplasmic reticulum membrane is crucial for the budding process, the identification of p7-lipid interactions could be important for understanding the HCV life cycle. Here, we report that p7 interacts with phosphatidylserine (PS) to induce membrane permeabilization. The interaction of p7 with PS was not inhibited by Gd ions, which have been known to interact with negatively charged lipids, but channel activity and p7-induced mitochondrial depolarization were inhibited by Gd ions. From the present results, we suggest that the p7-PS interaction plays an essential role in regulating its ion channel function and could be a potential molecular target for anti-HCV therapy.
丙型肝炎病毒 (HCV) p7 是一种已知的 HCV 成熟的非选择性阳离子通道。由于 HCV 蛋白与内质网膜中宿主脂质的相互作用对出芽过程至关重要，因此鉴定 p7-脂质相互作用对于理解 HCV 生命周期可能很重要。在这里，我们报告 p7 与磷脂酰丝氨酸 (PS) 相互作用诱导膜通透性。p7 与 PS 的相互作用不受已知与带负电荷的脂质相互作用的 Gd 离子抑制，但通道活性和 p7 诱导的线粒体去极化被 Gd 离子抑制。根据目前的结果，我们认为 p7-PS 相互作用在调节其离子通道功能中起着重要作用，可能是抗 HCV 治疗的潜在分子靶标。
