Function follows form: the structure of the N-terminal domain of HCV NS5A

Détails

ID Serval
serval:BIB_41A39CE720C2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Function follows form: the structure of the N-terminal domain of HCV NS5A
Périodique
Hepatology
Auteur⸱e⸱s
Moradpour  D., Brass  V., Penin  F.
ISSN
0270-9139 (Print)
Statut éditorial
Publié
Date de publication
09/2005
Volume
42
Numéro
3
Pages
732-5
Notes
Journal Article --- Old month value: Sep
Résumé
Hepatitis C virus (HCV) is a human pathogen affecting nearly 3% of the world's population. Chronic infections can lead to cirrhosis and liver cancer. The RNA replication machine of HCV is a multi-subunit membrane-associated complex. The nonstructural protein NS5A is an active component of HCV replicase, as well as a pivotal regulator of replication and a modulator of cellular processes ranging from innate immunity to dysregulated cell growth. NS5A is a large phosphoprotein (56-58 kd) with an amphipathic -helix at its amino terminus that promotes membrane association. After this helix region, NS5A is organized into 3 domains. The N-terminal domain (domain I) coordinates a single zinc atom per protein molecule. Mutations disrupting either the membrane anchor or zinc binding of NS5A are lethal for RNA replication. However, probing the role of NS5A in replication has been hampered by a lack of structural information about this multifunctional protein. Here we report the structure of NS5A domain I at 2.5-A resolution, which contains a novel fold, a new zinc-coordination motif, and a disulfide bond. We use molecular surface analysis to suggest the location of protein-, RNA-, and membrane-interaction sites.
Mots-clé
Binding Sites Disulfides/analysis Hepacivirus/*enzymology Models, Molecular Peptide Fragments/chemistry Protein Conformation RNA Replicase/chemistry Viral Nonstructural Proteins/*chemistry Zinc/metabolism
Pubmed
Création de la notice
25/01/2008 17:05
Dernière modification de la notice
20/08/2019 14:42
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