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J Virol. 2002 Dec;76(24):13088-93.

The hepatitis C virus RNA-dependent RNA polymerase membrane insertion sequence is a transmembrane segment.

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  • 1Department of Medicine II, University Hospital, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.


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.

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