Identification of new functional regions ...
Document type :
Compte-rendu et recension critique d'ouvrage
DOI :
PMID :
Title :
Identification of new functional regions in hepatitis C virus envelope glycoprotein E2
Author(s) :
Albecka, Anna [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Montserret, Roland [Auteur]
Institut de biologie et chimie des protéines [Lyon] [IBCP]
Krey, Thomas [Auteur]
Virologie Structurale
Tarr, Alexander W. [Auteur]
Diesis, Eric [Auteur]
Institut de biologie et chimie des protéines [Lyon] [IBCP]
Ball, Jonathan K. [Auteur]
Descamps, Véronique [Auteur]
Unité de Virologie clinique et fondamentale [UVCF]
Duverlie, Gilles [Auteur]
Unité de Virologie clinique et fondamentale [UVCF]
Rey, Felix [Auteur]
Virologie Structurale
Penin, François [Auteur]
Institut de biologie et chimie des protéines [Lyon] [IBCP]
Dubuisson, Jean [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Montserret, Roland [Auteur]
Institut de biologie et chimie des protéines [Lyon] [IBCP]
Krey, Thomas [Auteur]
Virologie Structurale
Tarr, Alexander W. [Auteur]
Diesis, Eric [Auteur]
Institut de biologie et chimie des protéines [Lyon] [IBCP]
Ball, Jonathan K. [Auteur]
Descamps, Véronique [Auteur]
Unité de Virologie clinique et fondamentale [UVCF]
Duverlie, Gilles [Auteur]
Unité de Virologie clinique et fondamentale [UVCF]
Rey, Felix [Auteur]
Virologie Structurale
Penin, François [Auteur]
Institut de biologie et chimie des protéines [Lyon] [IBCP]
Dubuisson, Jean [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Journal title :
Journal of Virology
Pages :
1777-92
Publisher :
American Society for Microbiology
Publication date :
2011-02
ISSN :
0022-538X
HAL domain(s) :
Chimie/Cristallographie
English abstract : [en]
Little is known about the structure of the envelope glycoproteins of hepatitis C virus (HCV). To identify new regions essential for the function of these glycoproteins, we generated HCV pseudoparticles (HCVpp) containing ...
Show more >Little is known about the structure of the envelope glycoproteins of hepatitis C virus (HCV). To identify new regions essential for the function of these glycoproteins, we generated HCV pseudoparticles (HCVpp) containing HCV envelope glycoproteins, E1 and E2, from different genotypes in order to detect intergenotypic incompatibilities between these two proteins. Several genotype combinations were nonfunctional for HCV entry. Of interest, a combination of E1 from genotype 2a and E2 from genotype 1a was nonfunctional in the HCVpp system. We therefore used this nonfunctional complex and the recently described structural model of E2 to identify new functional regions in E2 by exchanging protein regions between these two genotypes. The functionality of these chimeric envelope proteins in the HCVpp system and/or the cell-cultured infectious virus (HCVcc) was analyzed. We showed that the intergenotypic variable region (IgVR), hypervariable region 2 (HVR2), and another segment in domain II play a role in E1E2 assembly. We also demonstrated intradomain interactions within domain I. Importantly, we also identified a segment (amino acids [aa] 705 to 715 [segment 705-715]) in the stem region of E2, which is essential for HCVcc entry. Circular dichroism and nuclear magnetic resonance structural analyses of the synthetic peptide E2-SC containing this segment revealed the presence of a central amphipathic helix, which likely folds upon membrane binding. Due to its location in the stem region, segment 705-715 is likely involved in the reorganization of the glycoprotein complexes taking place during the fusion process. In conclusion, our study highlights new functional and structural regions in HCV envelope glycoprotein E2.Show less >
Show more >Little is known about the structure of the envelope glycoproteins of hepatitis C virus (HCV). To identify new regions essential for the function of these glycoproteins, we generated HCV pseudoparticles (HCVpp) containing HCV envelope glycoproteins, E1 and E2, from different genotypes in order to detect intergenotypic incompatibilities between these two proteins. Several genotype combinations were nonfunctional for HCV entry. Of interest, a combination of E1 from genotype 2a and E2 from genotype 1a was nonfunctional in the HCVpp system. We therefore used this nonfunctional complex and the recently described structural model of E2 to identify new functional regions in E2 by exchanging protein regions between these two genotypes. The functionality of these chimeric envelope proteins in the HCVpp system and/or the cell-cultured infectious virus (HCVcc) was analyzed. We showed that the intergenotypic variable region (IgVR), hypervariable region 2 (HVR2), and another segment in domain II play a role in E1E2 assembly. We also demonstrated intradomain interactions within domain I. Importantly, we also identified a segment (amino acids [aa] 705 to 715 [segment 705-715]) in the stem region of E2, which is essential for HCVcc entry. Circular dichroism and nuclear magnetic resonance structural analyses of the synthetic peptide E2-SC containing this segment revealed the presence of a central amphipathic helix, which likely folds upon membrane binding. Due to its location in the stem region, segment 705-715 is likely involved in the reorganization of the glycoprotein complexes taking place during the fusion process. In conclusion, our study highlights new functional and structural regions in HCV envelope glycoprotein E2.Show less >
Language :
Anglais
Popular science :
Non
Source :
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