A ligand-binding pocket in the dengue virus envelope glycoprotein
By Yorgo Modis, Steven A. Ogata, D. Clements, S. Harrison. Proceedings of the National Academy of Sciences of the United States of America, 2003
1,052 citations recorded by the source corpus.
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 β-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.
Subfields: Insect Science, Public Health, Environmental and Occupational Health
View Paper: https://www.semanticscholar.org/paper/8afc777e2917b11e404243a4caf4547daa74b048
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In Public Health, Environmental and Occupational Health
Citations in the corpus
- Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection (2016, neutral): “The E protein is formed by three domains: EDI, which is involved in the conformational changes required for viral entry, EDII, containing the fusion loop, and EDIII, which may be involved in binding to cellular receptors (24).”
- Structure of a flavivirus envelope glycoprotein in its low‐pH‐induced membrane fusion conformation (2004, background): “The class II fusion proteins, E of flaviviruses (Rey et al, 1995; Modis et al, 2003) and E1 of alphaviruses (Lescar et al, 2001), have been shown to be homologous in spite of the absence of sequence conservation, and display a molecular architecture completely different from that of class I…”
- Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion (2016, background): “Similarly, an increase in protein–protein contacts made by domain III has been observed in DENV E (21, 33) (from 826 to 1,315 Å(2)) and SFV E1 (24, 31) proteins (from 572 to 1,530 Å(2)).”
- Structure of the dengue virus envelope protein after membrane fusion (2004, background): “Structures have been determined for the ectodomains of three class II proteins in their prefusion state”
- Flaviviridae :T he Viruses and Their Replication (2007, background): “Residues that influence the pH threshold for membrane fusion surround this pocket (494).”
- Protein-Protein and Protein-Ligand Docking (2013, methodology): “As a polycationic polymer, it has a high affinity to associate macromolecules such as insulin, pDNA, siRNA, heparin, among others, with antigenic molecules, protecting them in turn from hydrolytic and enzymatic degradation [37].”