Interaction with membranes of the full C-terminal domain of protein NS4B from hepatitis C virus.

Hepatitis C virus (HCV) NS4B protein is a transmembrane highly hydrophobic protein responsible for many key aspects of the viral replication process. The C-terminal part of NS4B is essential for replication and is a potential target for HCV replication inhibitors. In this work we have carried out a study of the binding to and interaction with model biomembranes of a peptide corresponding to the C-terminal domain of NS4B, NS4B(Cter). We show that NS4B(Cter) partitions into phospholipid membranes, is capable of rupturing membranes even at very low peptide-to-lipid ratios and its membrane-activity is modulated by lipid composition. NS4B(Cter) is located in a shallow position in the membrane but it is able to affect the lipid environment from the membrane surface down to the hydrophobic core. Our results identify the C-terminal region of the HCV NS4B protein as a membrane interacting domain, and therefore directly implicated in the HCV life cycle and possibly in the formation of the membranous web.