Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

• Published in: Viruses Vol. 7; no. 7; pp. 4119 - 4130
• Main Authors: Hung, Yu-Fu, Schwarten, Melanie, Hoffmann, Silke, Willbold, Dieter, Sklan, Ella, Koenig, Bernd
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.07.2015; MDPI
• Subjects: amphipathic helix; Cell Membrane - metabolism; Cell Membrane - virology; curvature sensing; Dengue - metabolism; Dengue - virology; Dengue fever; Dengue virus; Dengue virus (DENV); Dengue Virus - chemistry; Dengue Virus - genetics; Dengue Virus - metabolism; Humans; Labeling; Lipids; Liposomes - metabolism; Localization; Membranes; Mutation; non-structural protein 4A (NS4A); peptide membrane interaction; Peptides; Protein Structure, Tertiary; Proteins; Spectrum analysis; Viral infections; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - metabolism; Viruses; Tel Aviv Israel; Germany; Israel; Dengue virus (DENV); peptide membrane interaction; amphipathic helix; curvature sensing; non-structural protein 4A (NS4A)
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v7072812

Dengue virus (DENV) is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A) is a vital component of the viral replication complex (RC) and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48) is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48) to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48) to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.