Jones, Christopher (2015) The N-terminal Helical Region of the Hepatitis C Virus p7 Protein is Critical for Infectious Virus Production. PLoS Pathogens, 11 (11). e1005297. ISSN 1553-7374

Abstract

The hepatitis C virus (HCV) p7 protein is required for infectious virus production. Although NMR structures of p7 have been reported, the location of secondary structural elements and orientation of the p7 transmembrane domains differ among models. Furthermore, the p7 structure-function relationship remains unclear. Here, extensive mutagenesis, coupled with infectious virus production phenotyping and molecular modeling support p7 plasticity and demonstrate that the N-terminal helical region plays a previously underappreciated, yet critical functional role. We further identify the importance of N-terminal region residues 6, 9 and 12 -- predicted to point toward the pore formed by p7 oligomerization. Interrogation of position 6 reveals a size constraint, whereas 9 and 12 provide a requisite polar environment, suggesting a role in cation recruitment. Together, these findings indicate that the p7 N-terminal helical region is critical for protein-protein interactions, ion channel activity and infectious HCV production.

Item Type:	Article
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/25884