Unusual architecture of the p7 channel from hepatitis C virus

Unusual architecture of the p7 channel from hepatitis C virus Nature 498, 7455 (2013). doi:10.1038/nature12283 Authors: Bo OuYang, Shiqi Xie, Marcelo J. Berardi, Xinhao Zhao, Jyoti Dev, Wenjing Yu, Bing Sun & James J. Chou The hepatitis C virus (HCV) has developed a small membrane protein, p7, which remarkably can self-assemble into a large channel complex that selectively conducts cations. We wanted to examine the structural solution that the viroporin adopts in order to achieve selective cation conduction, because p7 has no homology with any of the known prokaryotic or eukaryotic channel proteins. The activity of p7 can be inhibited by amantadine and rimantadine, which are potent blockers of the influenza M2 channel and licensed drugs against influenza infections. The adamantane derivatives have been used in HCV clinical trials, but large variation in drug efficacy among the various HCV genotypes has been difficult to explain without detailed molecular structures. Here we determine the structures of this HCV viroporin as well as its drug-binding site using the latest nuclear magnetic resonance (NMR) technologies. The structure exhibits an unusual mode of hexameric assembly, where the individual p7 monomers, i, not only interact with their immediate neighbours, but also reach farther to associate with the i+2 and i+3 monomers, forming a sophisticated, funnel-like architecture. The structure also points to a mechanism of cati...
Source: Nature - Category: Research Authors: Tags: Letter Source Type: research