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Structure of the immature dengue virus at low pH primes proteolytic maturation.

Authors
  • Yu, I-Mei
  • Zhang, Wei
  • Holdaway, Heather A
  • Li, Long
  • Kostyuchenko, Victor A
  • Chipman, Paul R
  • Kuhn, Richard J
  • Rossmann, Michael G
  • Chen, Jue
Type
Published Article
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Mar 28, 2008
Volume
319
Issue
5871
Pages
1834–1837
Identifiers
DOI: 10.1126/science.1153264
PMID: 18369148
Source
Medline
License
Unknown

Abstract

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.

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