Conserved determinants for membrane association of nonstructural protein 5A from hepatitis C virus and related viruses

Détails

ID Serval
serval:BIB_9E09723A603D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Conserved determinants for membrane association of nonstructural protein 5A from hepatitis C virus and related viruses
Périodique
Journal of Virology
Auteur(s)
Brass  V., Pal  Z., Sapay  N., Deleage  G., Blum  H. E., Penin  F., Moradpour  D.
ISSN
0022-538X (Print)
Statut éditorial
Publié
Date de publication
03/2007
Volume
81
Numéro
6
Pages
2745-57
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Résumé
Nonstructural protein 5A (NS5A) is a membrane-associated essential component of the hepatitis C virus (HCV) replication complex. An N-terminal amphipathic alpha helix mediates in-plane membrane association of HCV NS5A and at the same time is likely involved in specific protein-protein interactions required for the assembly of a functional replication complex. The aim of this study was to identify the determinants for membrane association of NS5A from the related GB viruses and pestiviruses. Although primary amino acid sequences differed considerably, putative membrane anchor domains with amphipathic features were predicted in the N-terminal domains of NS5A proteins from these viruses. Confocal laser scanning microscopy, as well as membrane flotation analyses, demonstrated that NS5As from GB virus B (GBV-B), GBV-C, and bovine viral diarrhea virus, the prototype pestivirus, display membrane association characteristics very similar to those of HCV NS5A. The N-terminal 27 to 33 amino acid residues of these NS5A proteins were sufficient for membrane association. Circular dichroism analyses confirmed the capacity of these segments to fold into alpha helices upon association with lipid-like molecules. Despite structural conservation, only very limited exchanges with sequences from related viruses were tolerated in the context of functional HCV RNA replication, suggesting virus-specific interactions of these segments. In conclusion, membrane association of NS5A by an N-terminal amphipathic alpha helix is a feature shared by HCV and related members of the family Flaviviridae. This observation points to conserved roles of the N-terminal amphipathic alpha helices of NS5A in replication complex formation.
Mots-clé
Amino Acid Sequence Amino Acids/chemistry Animals Cattle Cell Line, Tumor Cell Membrane/*metabolism Circular Dichroism Conserved Sequence Diarrhea Viruses, Bovine Viral/*chemistry Electroporation GB virus A/*chemistry GB virus B/*chemistry Humans Molecular Sequence Data Osteosarcoma/pathology Peptides/chemistry Protein Biosynthesis Protein Structure, Secondary Protein Structure, Tertiary Tetracycline/pharmacology Transfection Viral Nonstructural Proteins/*chemistry
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 16:06
Dernière modification de la notice
20/08/2019 15:04
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