The stem region of premembrane protein plays an important role in the virus surface protein rearrangement during dengue maturation

Qian Zhang, Cornelia Hunke, Yin Hoe Yau, Vernon Seow, Sumarlin Lee, Lukas Bahati Tanner, Xue Li Guan, Markus R. Wenk, Guntur Fibriansah, Pau Ling Chew, Petra Kukkaro, Goran Biuković, Pei Yong Shi, Susana Geifman Shochat, Gerhard Grüber, Shee Mei Lok

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Newly assembled dengue viruses (DENV) undergo maturation to become infectious particles. The maturation process involves major rearrangement of virus surface premembrane (prM) and envelope (E) proteins. The prM-E complexes on immature viruses are first assembled as trimeric spikes in the neutral pH environment of the endoplasmic reticulum. When the virus is transported to the low pH environment of the exosomes, these spikes rearrange into dimeric structures, which lie parallel to the virus lipid envelope. The proteins involved in driving this process are unknown. Previous cryoelectron microscopy studies of the mature DENV showed that the prM-stem region (residues 111-131) is membrane-associated and may interact with the E proteins. Here we investigated the prMstem region in modulating the virus maturation process. The binding of the prM-stem region to the E protein was shown to increase significantly at low pH compared with neutral pH in ELISAs and surface plasmon resonance studies. In addition, the affinity of the prM-stem region for the liposome, as measured by fluorescence correlation spectroscopy, was also increased when pH is lowered. These results suggest that the prM-stem region forms a tight association with the virus membrane and attracts the associated E protein in the low pH environment of exosomes. This will lead to the surface protein rearrangement observed during maturation.

Original languageEnglish (US)
Pages (from-to)40525-40534
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number48
DOIs
StatePublished - Nov 23 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Zhang, Q., Hunke, C., Yau, Y. H., Seow, V., Lee, S., Tanner, L. B., Guan, X. L., Wenk, M. R., Fibriansah, G., Chew, P. L., Kukkaro, P., Biuković, G., Shi, P. Y., Shochat, S. G., Grüber, G., & Lok, S. M. (2012). The stem region of premembrane protein plays an important role in the virus surface protein rearrangement during dengue maturation. Journal of Biological Chemistry, 287(48), 40525-40534. https://doi.org/10.1074/jbc.M112.384446