Palomares-Jerez M Francisca, Nemesio Henrique, Villalaín José
Universidad Miguel Hernandez, Eliche-Alicante, Spain.
Biochim Biophys Acta. 2012 Nov;1818(11):2536-49. doi: 10.1016/j.bbamem.2012.06.012. Epub 2012 Jun 27.
Hepatitis C virus (HCV) NS4B protein is a transmembrane highly hydrophobic protein responsible for many key aspects of the viral replication process. The C-terminal part of NS4B is essential for replication and is a potential target for HCV replication inhibitors. In this work we have carried out a study of the binding to and interaction with model biomembranes of a peptide corresponding to the C-terminal domain of NS4B, NS4B(Cter). We show that NS4B(Cter) partitions into phospholipid membranes, is capable of rupturing membranes even at very low peptide-to-lipid ratios and its membrane-activity is modulated by lipid composition. NS4B(Cter) is located in a shallow position in the membrane but it is able to affect the lipid environment from the membrane surface down to the hydrophobic core. Our results identify the C-terminal region of the HCV NS4B protein as a membrane interacting domain, and therefore directly implicated in the HCV life cycle and possibly in the formation of the membranous web.
丙型肝炎病毒（HCV）NS4B蛋白是一种跨膜高度疏水蛋白，负责病毒复制过程的许多关键方面。NS4B的C末端部分对复制至关重要，是HCV复制抑制剂的潜在靶点。在这项工作中，我们对与NS4B C末端结构域对应的肽NS4B（Cter）与模型生物膜的结合及相互作用进行了研究。我们发现NS4B（Cter）可分配到磷脂膜中，即使在肽与脂质比例非常低的情况下也能使膜破裂，并且其膜活性受脂质组成调节。NS4B（Cter）位于膜中的浅位置，但它能够从膜表面直至疏水核心影响脂质环境。我们的结果确定HCV NS4B蛋白的C末端区域为膜相互作用结构域，因此直接参与HCV生命周期，可能还参与膜网的形成。
