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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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
Issue number7
StatePublished - 21 Jul 2015


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


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