Amphipathic alpha-helix AH2 is a major determinant for the oligomerization of hepatitis C virus nonstructural protein 4B.

Details

Serval ID
serval:BIB_F40245B561D1
Type
Article: article from journal or magazin.
Collection
Publications
Title
Amphipathic alpha-helix AH2 is a major determinant for the oligomerization of hepatitis C virus nonstructural protein 4B.
Journal
Journal of Virology
Author(s)
Gouttenoire J., Roingeard P., Penin F., Moradpour D.
ISSN
1098-5514[electronic], 0022-538X[linking]
Publication state
Published
Issued date
2010
Volume
84
Number
24
Pages
12529-12537
Language
english
Abstract
Nonstructural protein 4B (NS4B) is a key organizer of hepatitis C virus (HCV) replication complex formation. It induces a specific membrane rearrangement, designated membranous web, that serves as a scaffold for the HCV replication complex. However, the mechanisms underlying membranous web formation are poorly understood. Based on fluorescence resonance energy transfer (FRET) and confirmatory coimmunoprecipitation analyses, we provide evidence for an oligomerization of NS4B in the membrane environment of intact cells. Several conserved determinants were found to be involved in NS4B oligomerization, through homotypic and heterotypic interactions. N-terminal amphipathic ?-helix AH2, comprising amino acids 42 to 66, was identified as a major determinant for NS4B oligomerization. Mutations that affected the oligomerization of NS4B disrupted membranous web formation and HCV RNA replication, implying that oligomerization of NS4B is required for the creation of a functional replication complex. These findings enhance our understanding of the functional architecture of the HCV replication complex and may provide new angles for therapeutic intervention. At the same time, they expand the list of positive-strand RNA virus replicase components acting as oligomers.
Pubmed
Web of science
Open Access
Yes
Create date
14/12/2010 17:36
Last modification date
20/08/2019 17:20
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