Amino terminal region of dengue virus NS4A cytosolic domain binds to highly curved liposomes

Yu Fu Hung, Melanie Schwarten, Silke Hoffmann, Dieter Willbold, Ella H. Sklan, Bernd W. Koenig

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4119-4130
Number of pages12
JournalViruses
Volume7
Issue number7
DOIs
StatePublished - 21 Jul 2015

Keywords

  • Amphipathic helix
  • Curvature sensing
  • Dengue virus (DENV)
  • Non-structural protein 4A (NS4A)
  • Peptide membrane interaction

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