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Fusogenic properties of the Ectodomain of HCV E2 envelope protein

机译:HCV E2包络蛋白外构域的致致骨髓性特性

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The steps leading from hepatitis C virus (HCV) attachment to the hepatocytes to the fusion of viral and cellular membranes remain uncharacterized. In this regard, we have studied the mechanism underlying the HCV fusion process using liposomes and a truncated form of E2 protein lacking the transmembrane region, E2661 (amino acids 384-661). E2661 has been previously obtained by using the baculovirus expression system and shown to behave as an independent folding domain (M. Rodriguez-Rodriguez, D. Tello, B. Yelamos, J. Gomez-Gutierrez, B. Pacheco, S. Ortega, A.G. Serrano, D.L. Peterson, F. Gavilanes, Structural properties of the ectodomain of hepatitis C virus E2 envelope protein, Virus Res. 139 (2009) 91-99). This form has been used in lipid-protein interaction studies with different model vesicles, at different pHs and by employing a variety of fluorescent assays. The obtained results indicate that E2661 induces vesicle aggregation, lipid mixing and liposome leakage, reaching higher values in the presence of negatively charged phospholipids and cholesterol at acidic pH. Therefore, the results of these studies would be indicative of an HCV infection process through receptor mediated endocytosis. Accordingly, E2 might be important in the HCV initial infective steps, interacting with the target membranes and giving rise to their subsequent destabilization.
机译:从丙型肝炎病毒(HCV)附着到肝细胞病毒与细胞膜的融合导致的步骤仍然未表征。在这方面,我们已经研究了使用脂质体中的HCV融合过程背后的机理和E2蛋白的缺乏跨膜区域,E2661(氨基酸384-661)的截短形式。 E2661已通过使用杆状病毒表达系统被先前获得的,并显示出表现为一个独立的折叠结构域(M.罗德里格斯-Rodriguez的,D.特洛,B. Yelamos,J.戈麦斯-Gutierrez的,B.帕切科,S.特加,AG拉诺,DL彼得森,F.加维拉内斯,C型肝炎病毒E2包膜蛋白,病毒研究的胞外域的结构特性。139(2009)91-99)。这种形式已经结合不同的模型囊泡,在不同pH的脂质 - 蛋白质相互作用研究并且通过采用各种荧光测定法中使用。将所得到的结果表明,E2661诱导囊泡聚集,脂质混合和脂质体的泄漏,在带负电荷的磷脂和胆固醇的在酸性pH下存在达到更高的值。因此,这些研究的结果将是通过受体介导的内吞作用表示HCV感染的过程。因此,E2可能在HCV感染初期的重要步骤,有目标膜相互作用,并引起他们的后续不稳定。

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