TY  - JOUR
AU  - Hung, Yu-Fu
AU  - Schwarten, Melanie
AU  - Schünke, Sven
AU  - Thiagarajan-Rosenkranz, Pallavi
AU  - Hoffmann, Silke
AU  - Sklan, Ella H.
AU  - Willbold, Dieter
AU  - König, Bernd
TI  - Dengue virus NS4A cytoplasmic domain binding to liposomes is sensitive to membrane curvature
JO  - Biochimica et biophysica acta / Biomembranes
VL  - 1848
IS  - 5
SN  - 0005-2736
CY  - Amsterdam
PB  - Elsevier
M1  - FZJ-2015-05136
SP  - 1119 - 1126
PY  - 2015
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000352041100006
DO  - DOI:10.1016/j.bbamem.2015.01.015
UR  - https://juser.fz-juelich.de/record/203112
ER  -