Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A.

Details

Serval ID
serval:BIB_3678C054F57B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A.
Journal
Journal of Biological Chemistry
Author(s)
Penin F., Brass V., Appel N., Ramboarina S., Montserret R., Ficheux D., Blum H.E., Bartenschlager R., Moradpour D.
ISSN
0021-9258
Publication state
Published
Issued date
09/2004
Peer-reviewed
Oui
Volume
279
Number
39
Pages
40835-40843
Language
english
Notes
Publication types: Journal Article
Abstract
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a membrane-associated, essential component of the viral replication complex. Here, we report the three-dimensional structure of the membrane anchor domain of NS5A as determined by NMR spectroscopy. An alpha-helix extending from amino acid residue 5 to 25 was observed in the presence of different membrane mimetic media. This helix exhibited a hydrophobic, Trprich side embedded in detergent micelles, while the polar, charged side was exposed to the solvent. Thus, the NS5A membrane anchor domain forms an in-plane amphipathic alpha-helix embedded in the cytosolic leaflet of the membrane bilayer. Interestingly, mutations affecting the positioning of fully conserved residues located at the cytosolic surface of the helix impaired HCV RNA replication without interfering with the membrane association of NS5A. In conclusion, the NS5A membrane anchor domain constitutes a unique platform that is likely involved in specific interactions essential for the assembly of the HCV replication complex and that may represent a novel target for antiviral intervention.
Keywords
Amino Acid Sequence, Antibodies, Monoclonal/chemistry, Cell Line, Tumor, Cell Membrane/metabolism, Cytosol/metabolism, Humans, Lipid Bilayers/chemistry, Magnetic Resonance Spectroscopy, Micelles, Microscopy, Confocal, Models, Molecular, Molecular Sequence Data, Mutation, Peptides/chemistry, Plasmids/metabolism, Protein Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, Transcription, Genetic, Transfection, Viral Nonstructural Proteins/chemistry, Viral Nonstructural Proteins/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 16:05
Last modification date
20/08/2019 13:24
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