A toggle switch controls the low pH-triggered rearrangement and maturation of the dengue virus envelope proteins

Aihua Zheng, Fei Yuan, Lara M. Kleinfelter, Margaret Kielian

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Immature dengue virus particles undergo a dramatic conformational change upon exposure to the acidic environment of the late secretory pathway. The interactions of the E fusion proteins and prM chaperone proteins on the virus envelope are reorganized to permit prM processing by a host protease, furin, thus priming virus for fusion and infection. Here we identify a pH-dependent toggle switch that controls this key conformational change during virus maturation. Our data show that the M region of prM interacts with E at neutral pH but is released at acidic pH, while the pr region interacts with E at acidic pH but is released at neutral pH. Alanine substitution of the conserved residue H98 in prM disrupts the switch by inhibiting dissociation of M from E at low pH, resulting in impaired prM processing and decreased virus infectivity. Thus, release of M-E interaction at low pH promotes formation of a furin-accessible intermediate.

Original languageEnglish (US)
Article number3877
JournalNature communications
Volume5
DOIs
StatePublished - May 20 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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