Abstract
Dengue virus is an emerging global health threat. Its major envelope glycoprotein, E, mediates viral attachment and entry by membrane fusion. A crystal structure of the soluble ectodomain of E from dengue virus type 2 reveals a hydrophobic pocket lined by residues that influence the pH threshold for fusion. The pocket, which accepts a hydrophobic ligand, opens and closes through a conformational shift in a beta-hairpin at the interface between two domains. These features point to a structural pathway for the fusion-activating transition and suggest a strategy for finding small-molecule inhibitors of dengue and other flaviviruses.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites
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Crystallography, X-Ray
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Dengue Virus / genetics
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Dengue Virus / metabolism*
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Dengue Virus / pathogenicity
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Dengue Virus / physiology
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Dimerization
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Humans
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Ligands
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Membrane Fusion
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Models, Molecular
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Protein Structure, Quaternary
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Protein Subunits
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Viral Envelope Proteins / chemistry*
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / metabolism*
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Virus Assembly
Substances
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E-glycoprotein, Dengue virus type 2
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Ligands
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Peptide Fragments
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Protein Subunits
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Recombinant Proteins
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Viral Envelope Proteins