Journal
JOURNAL OF VIROLOGY
Volume 80, Issue 23, Pages 11467-11474Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01125-06
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Funding
- NCRR NIH HHS [RR 07707, P41 RR007707] Funding Source: Medline
- NIAID NIH HHS [AI 061373, U01 AI061373] Funding Source: Medline
- NIGMS NIH HHS [T32 GM 07200, T32 GM007200, T32 GM 008492, T32 GM008492] Funding Source: Medline
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The envelope glycoprotein (E) of West Nile virus (WNV) undergoes a conformational rearrangement triggered by low pH that results in a class II fusion event required for viral entry. Herein we present the 3.0-angstrom crystal structure of the ectodomain of WNV E, which reveals insights into the flavivirus life cycle. We found that WNV E adopts a three-domain architecture that is shared by the E proteins from dengue and tick-borne encephalitis viruses and forms a rod-shaped configuration similar to that observed in immature flavivirus particles. Interestingly, the single N-linked glycosylation site on WNV E is displaced by a novel alpha-helix, which could potentially alter lectin-mediated attachment. The localization of histidines within the hinge regions of E implicates these residues in pH-induced conformational transitions. Most strikingly, the WNV E ectodomain crystallized as a monomer, in contrast to other flavivirus E proteins, which have crystallized as antiparallel dimers. WNV E assembles in a crystalline lattice of perpendicular molecules, with the fusion loop of one E protein buried in a hydrophobic pocket at the DI-DIII interface of another. Dimeric E proteins pack their fusion loops into analogous pockets at the dimer interface. We speculate that E proteins could pivot around the fusion loop-pocket junction, allowing virion conformational transitions while minimizing fusion loop exposure.
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