%0 Journal Article
%A Hung, Yu-Fu
%A Schwarten, Melanie
%A Schünke, Sven
%A Thiagarajan-Rosenkranz, Pallavi
%A Hoffmann, Silke
%A Sklan, Ella H.
%A Willbold, Dieter
%A König, Bernd
%T Dengue virus NS4A cytoplasmic domain binding to liposomes is sensitive to membrane curvature
%J Biochimica et biophysica acta / Biomembranes
%V 1848
%N 5
%@ 0005-2736
%C Amsterdam
%I Elsevier
%M FZJ-2015-05136
%P 1119 - 1126
%D 2015
%X Dengue virus (DENV) infection is a growing public health threat with more than one-third of the world's population at risk. Non-structural protein 4A (NS4A), one of the least characterized viral proteins, is a highly hydrophobic transmembrane protein thought to induce the membrane alterations that harbor the viral replication complex. The NS4A N-terminal (amino acids 1–48), has been proposed to contain an amphipathic α-helix (AH). Mutations (L6E; M10E) designed to reduce the amphipathic character of the predicted AH, abolished viral replication and reduced NS4A oligomerization. Nuclear magnetic resonance (NMR) spectroscopy was used to characterize the N-terminal cytoplasmic region (amino acids 1–48) of both wild type and mutant NS4A in the presence of SDS micelles. Binding of the two N-terminal NS4A peptides to liposomes was studied as a function of membrane curvature and lipid composition. The NS4A N-terminal was found to contain two AHs separated by a non-helical linker. The abovementioned mutations did not significantly affect the helical secondary structure of this domain. However, they reduced the affinity of the N-terminal NS4A domain for lipid membranes. Binding of wild type NS4A(1–48) to liposomes is highly dependent on membrane curvature.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000352041100006
%R 10.1016/j.bbamem.2015.01.015
%U https://juser.fz-juelich.de/record/203112