title: Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes.
abstract: 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.
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich,52425 Jülich, Germany. y.hung@fz-juelich.de.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1,40255 Düsseldorf, Germany. y.hung@fz-juelich.de.
authors.forename: Yu-Fu
authors.initials: YF
authors.lastname: Hung
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich,52425 Jülich, Germany. m.schwarten@fz-juelich.de.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schwarten
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich,52425 Jülich, Germany. si.hoffmann@fz-juelich.de.
authors.forename: Silke
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich,52425 Jülich, Germany. d.willbold@fz-juelich.de.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1,40255 Düsseldorf, Germany. d.willbold@fz-juelich.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.affiliation: Department Clinical Microbiology and Immunology, Sackler School of Medicine,Tel Aviv University, Tel Aviv 69978, Israel. sklan@post.tau.ac.il.
authors.forename: Ella H
authors.initials: EH
authors.lastname: Sklan
authors.affiliation: Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich,52425 Jülich, Germany. b.koenig@fz-juelich.de.|Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1,40255 Düsseldorf, Germany. b.koenig@fz-juelich.de.
authors.forename: BerndW
authors.initials: B
authors.lastname: Koenig
mesh_terms: D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D003715:Dengue / Q000378:metabolism / Q000821:virology*; D003716:Dengue Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D008081:Liposomes; C000601110:NS4A protein, Dengue virus; D017361:Viral Nonstructural Proteins
keywords: Dengue virus (DENV); amphipathic helix; curvature sensing; non-structural protein 4A (NS4A); peptide membrane interaction