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

Détails

ID Serval
serval:BIB_7EAE6077AF4E
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
Structure-function analyses of NS4B, an essential component of the hepatitis C virus replication complex
Titre de la conférence
Annual meeting of the Swiss Society of Gastroenterology, Swiss Society for Visceral Surgery, Swiss Association for the Study of the Liver
Auteur(s)
Gouttenoire J., Kennel A., Montserret R., Bellecave P., Penin F., Moradpour D.
Organisation
Annual Meeting of the Swiss Society of Gastroenterology
Adresse
Zurich, Switzerland, September 17-18, 2009
ISSN
1424-7860
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
139
Série
Swiss Medical Weekly
Pages
7S
Langue
anglais
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.
Création de la notice
01/10/2015 15:21
Dernière modification de la notice
21/08/2019 6:34
Données d'usage