1OK8

Crystal structure of the dengue 2 virus envelope glycoprotein in the postfusion conformation

Summary for 1OK8

• Entry DOI: 10.2210/pdb1ok8/pdb
• Related: 1L9K 1OAM 1OAN
• Descriptor: MAJOR ENVELOPE PROTEIN E, 2-acetamido-2-deoxy-beta-D-glucopyranose, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: viral protein, membrane fusion, flavivirus, fusion peptide, low-ph conformational change, class 2 fusion protein
• Biological source: DENGUE VIRUS TYPE 2
• Cellular location: Capsid protein C: Virion (Potential). Peptide pr: Secreted (By similarity). Small envelope protein M: Virion membrane; Multi-pass membrane protein (By similarity). Envelope protein E: Virion membrane; Multi- pass membrane protein (By similarity). Non-structural protein 1: Secreted. Non-structural protein 2A-alpha: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Non-structural protein 2A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): P12823
• Total number of polymer chains: 1
• Total formula weight: 44076.05

Authors

Modis, Y.,Harrison, S.C. (deposition date: 2003-07-19, release date: 2004-01-29, Last modification date: 2024-10-23)

Primary citation

Modis, Y.,Ogata, S.,Clements, D.,Harrison, S.C.
Structure of the Dengue Virus Envelope Protein After Membrane Fusion
Nature, 427:313-, 2004

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.

PubMed: 14737159
DOI: 10.1038/NATURE02165

Experimental method

X-RAY DIFFRACTION (2 Å)