The Membrane Anchor of GB virus B Nonstructural Protein 5B Can Substitute the Hepatitis C Virus NS5B Transmembrane Domain: Implications for a Conserved Protein Interaction Site

Background and aim: Hepatitis C virus (HCV) nonstructural proteins form a membrane-associated replication complex. HCV Nonstructural protein 5B (NS5B), the viral RNA-dependent RNA polymerase (RdRp), is a tail-anchored protein with a highly conserved C-terminal transmembrane domain (TMD) that is required for the assembly of a functional replication complex. The aim of this study was to further validate the function of the NS5B TMD in the process of replication complex formation. Methodology: Systematic sequence comparisons and predictions of transmembrane segments were coupled with biochemical analyses to identif…