Structure-function analyses of NS4B, an essential component of the hepatitis C virus replication complex

Details

Serval ID
serval:BIB_7EAE6077AF4E
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Title
Structure-function analyses of NS4B, an essential component of the hepatitis C virus replication complex
Title of the conference
Annual meeting of the Swiss Society of Gastroenterology, Swiss Society for Visceral Surgery, Swiss Association for the Study of the Liver
Author(s)
Gouttenoire J., Kennel A., Montserret R., Bellecave P., Penin F., Moradpour D.
Organization
Annual Meeting of the Swiss Society of Gastroenterology
Address
Zurich, Switzerland, September 17-18, 2009
ISSN
1424-7860
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
139
Series
Swiss Medical Weekly
Pages
7S
Language
english
Notes
B a c k g r o u n d: Nonstructural protein 4B (NS4B) plays anessential role in the formation of the hepatitis C virus (HCV)replication complex. It is an integral membrane protein that hasonly poorly been characterized to date, believed to comprise acentral part harboring 4 transmembrane passages (TM) flankedby 2 cytosolic parts. However, a precise membrane topology ofHCV NS4B is thus far elusive. This work is aimed at enhancingour understanding of the structure and function of this protein.Methods: Full-length NS4B as well as a comprehensive panelof mutants were fused to the green fluorescent protein andexpressed in cultured cells. The impact of point mutations onHCV infection and replication was assessed by the use of cellculture-derived HCV and the replicon system. 3-D structureswere determined by nuclear magnetic resonance. Proteinproteininteractions were investigated by fluorescenceresonance energy transfer and co-immunoprecipitation.R e s u l t s : We identified two unexpected determinants formembrane association in the N- and C-terminal parts of HCVNS4B. The first determinant is an amphipathic alpha-helix thatcan traverse the membrane, likely as an oligomer, therebyconstituting a fifth TM. The second is a peculiar "twisted"amphipathic alpha-helix at the C-terminus of NS4B. Bothdeterminants are involved in protein-protein interactions andplay important roles in the formation of replication complex.Conclusions: These results provide the first atomic resolutionstructures of essential membrane-associated segments ofNS4B and highlight their essential roles in the assembly of afunctional HCV replication complex.
Create date
01/10/2015 15:21
Last modification date
21/08/2019 6:34
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