title: The hepatitis C virus RNA-dependent RNA polymerase membrane insertion sequence is a transmembrane segment.
abstract: 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.
authors.affiliation: Department of Medicine II, University Hospital, University of Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Ivashkina
authors.forename: Benno
authors.initials: B
authors.lastname: Wölk
authors.forename: Volker
authors.initials: V
authors.lastname: Lohmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Bartenschlager
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.forename: François
authors.initials: F
authors.lastname: Penin
authors.forename: Darius
authors.initials: D
authors.lastname: Moradpour
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D016174:Hepacivirus / Q000502:physiology; D017433:Protein Structure, Secondary; D012367:RNA, Viral / Q000096:biosynthesis; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase