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Science 28 March 2008:
Vol. 319. no. 5871, pp. 1834 - 1837
DOI: 10.1126/science.1153264
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Reports

Structure of the Immature Dengue Virus at Low pH Primes Proteolytic Maturation

I-Mei Yu, Wei Zhang, Heather A. Holdaway, Long Li, Victor A. Kostyuchenko, Paul R. Chipman, Richard J. Kuhn, Michael G. Rossmann, Jue Chen*

Intracellular cleavage of immature flaviviruses is a critical step in assembly that generates the membrane fusion potential of the E glycoprotein. With cryo–electron microscopy we show that the immature dengue particles undergo a reversible conformational change at low pH that renders them accessible to furin cleavage. At a pH of 6.0, the E proteins are arranged in a herringbone pattern with the pr peptides docked onto the fusion loops, a configuration similar to that of the mature virion. After cleavage, the dissociation of pr is pH-dependent, suggesting that in the acidic environment of the trans-Golgi network pr is retained on the virion to prevent membrane fusion. These results suggest a mechanism by which flaviviruses are processed and stabilized in the host cell secretory pathway.

Department of Biological Sciences, 915 West State Street, Purdue University, West Lafayette, IN 47907–2054, USA.

* To whom correspondence should be addressed. E-mail: chenjue{at}purdue.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Differential Modulation of prM Cleavage, Extracellular Particle Distribution, and Virus Infectivity by Conserved Residues at Nonfurin Consensus Positions of the Dengue Virus pr-M Junction.
J. Junjhon, M. Lausumpao, S. Supasa, S. Noisakran, A. Songjaeng, P. Saraithong, K. Chaichoun, U. Utaipat, P. Keelapang, A. Kanjanahaluethai, et al. (2008)
J. Virol. 82, 10776-10791
   Abstract »    Full Text »    PDF »
Identification of specific histidines as pH sensors in flavivirus membrane fusion.
R. Fritz, K. Stiasny, and F. X. Heinz (2008)
J. Cell Biol. 183, 353-361
   Abstract »    Full Text »    PDF »
The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation.
L. Li, S.-M. Lok, I-M. Yu, Y. Zhang, R. J. Kuhn, J. Chen, and M. G. Rossmann (2008)
Science 319, 1830-1834
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)