Ivashkina Natalia, Wölk Benno, Lohmann Volker, Bartenschlager Ralf, Blum Hubert E, Penin François, Moradpour Darius
Department of Medicine II, University Hospital, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
J Virol. 2002 Dec;76(24):13088-93. doi: 10.1128/jvi.76.24.13088-13093.2002.
The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) belongs to a class of membrane proteins termed tail-anchored proteins. Here, we show that the HCV RdRp C-terminal membrane insertion sequence traverses the phospholipid bilayer as a transmembrane segment. Moreover, the HCV RdRp was found to be retained in the endoplasmic reticulum (ER) or an ER-derived modified compartment both following transient transfection and in the context of a subgenomic replicon. An absolutely conserved GVG motif was not essential for membrane insertion but possibly provides a docking site for transmembrane protein-protein interactions. These findings have important implications for the functional architecture of the HCV replication complex.
丙型肝炎病毒（HCV）的RNA依赖性RNA聚合酶（RdRp）属于一类被称为尾锚定蛋白的膜蛋白。在此，我们表明HCV RdRp的C末端膜插入序列作为跨膜片段穿过磷脂双层。此外，无论是在瞬时转染后还是在亚基因组复制子的背景下，都发现HCV RdRp保留在内质网（ER）或源自ER的修饰区室中。一个绝对保守的GVG基序对膜插入并非必不可少，但可能为跨膜蛋白-蛋白相互作用提供一个对接位点。这些发现对HCV复制复合体的功能结构具有重要意义。
