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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cryoelectron Microscopy
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Crystallography, X-Ray
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Dengue Virus / chemistry*
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Dengue Virus / growth & development
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Dengue Virus / metabolism
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Dengue Virus / ultrastructure*
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Dimerization
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Endoplasmic Reticulum / virology
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Furin / metabolism
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Hydrogen-Ion Concentration
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Image Processing, Computer-Assisted
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Membrane Fusion
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Protein Conformation
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Viral Envelope Proteins / chemistry*
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Viral Envelope Proteins / metabolism
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Viral Fusion Proteins / chemistry
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Viral Fusion Proteins / metabolism
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Viral Matrix Proteins / chemistry*
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Viral Matrix Proteins / metabolism
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Virion / metabolism
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Virion / ultrastructure
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trans-Golgi Network / metabolism
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trans-Golgi Network / virology
Substances
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E-glycoprotein, Dengue virus type 2
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Viral Envelope Proteins
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Viral Fusion Proteins
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Viral Matrix Proteins
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Furin