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- Title
Cryo-EM structure of the mature dengue virus at 3.5-Å resolution.
- Authors
Zhang, Xiaokang; Ge, Peng; Yu, Xuekui; Brannan, Jennifer M; Bi, Guoqiang; Zhang, Qinfen; Schein, Stan; Zhou, Z Hong
- Abstract
Regulated by pH, membrane-anchored proteins E and M function during dengue virus maturation and membrane fusion. Our atomic model of the whole virion from cryo-electron microscopy at 3.5-Å resolution reveals that in the mature virus at neutral extracellular pH, the N-terminal 20-amino-acid segment of M (involving three pH-sensing histidines) latches and thereby prevents spring-loaded E fusion protein from prematurely exposing its fusion peptide. This M latch is fastened at an earlier stage, during maturation at acidic pH in the trans-Golgi network. At a later stage, to initiate infection in response to acidic pH in the late endosome, M releases the latch and exposes the fusion peptide. Thus, M serves as a multistep chaperone of E to control the conformational changes accompanying maturation and infection. These pH-sensitive interactions could serve as targets for drug discovery.
- Subjects
HYDROGEN-ion concentration; ACIDITY; MEMBRANE proteins; DENGUE viruses; MEMBRANE fusion; MOLECULAR chaperones
- Publication
Nature Structural & Molecular Biology, 2013, Vol 20, Issue 1, p105
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2463