Download MendeleyStructure of the Dengue Virus Envelope Protein After Membrane Fusion
Modis, Y., Ogata, S., Clements, D., Harrison, S.C.(2004) Nature 427: 313
- PubMed: 14737159
- DOI: https://doi.org/10.1038/nature02165
- Primary Citation of Related Structures:
1OK8 - PubMed Abstract:
Dengue virus enters a host cell when the viral envelope glycoprotein, E, binds to a receptor and responds by conformational rearrangement to the reduced pH of an endosome. The conformational change induces fusion of viral and host-cell membranes. A three-dimensional structure of the soluble E ectodomain (sE) in its trimeric, postfusion state reveals striking differences from the dimeric, prefusion form. The elongated trimer bears three 'fusion loops' at one end, to insert into the host-cell membrane. Their structure allows us to model directly how these fusion loops interact with a lipid bilayer. The protein folds back on itself, directing its carboxy terminus towards the fusion loops. We propose a fusion mechanism driven by essentially irreversible conformational changes in E and facilitated by fusion-loop insertion into the outer bilayer leaflet. Specific features of the folded-back structure suggest strategies for inhibiting flavivirus entry.
Organizational Affiliation:
Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
