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Journal of Virology, December 2002, p. 13088-13093, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.13088-13093.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Hepatitis C Virus RNA-Dependent RNA Polymerase Membrane Insertion Sequence Is a Transmembrane Segment

Natalia Ivashkina,1 Benno Wölk,1 Volker Lohmann,2 Ralf Bartenschlager,2 Hubert E. Blum,1 François Penin,3 and Darius Moradpour1*

Department of Medicine II, University of Freiburg, D-79106 Freiburg,1 Department of Molecular Virology, University of Heidelberg, D-69120 Heidelberg, Germany,2 Institut de Biologie et Chimie des Protéines, CNRS-UMR 5086, F-69367 Lyon Cedex 07, France3

Received 17 June 2002/ Accepted 3 September 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.

* Corresponding author. Mailing address: Department of Medicine II, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany. Phone: 49 761 270 3510. Fax: 49 761 270 3610. E-mail: Darius.Moradpour{at}uni-freiburg.de.

Journal of Virology, December 2002, p. 13088-13093, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.13088-13093.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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