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Journal of Virology, December 2006, p. 11467-11474, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01125-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Crystal Structure of the West Nile Virus Envelope Glycoprotein{triangledown}

Grant E. Nybakken,1 Christopher A. Nelson,1 Beverly R. Chen,1 Michael S. Diamond,1,2,3 and Daved H. Fremont1,4*

Departments of Pathology and Immunology,1 Medicine,2 Molecular Microbiology,3 Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 631104

Received 1 June 2006/ Accepted 1 September 2006

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-Å 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.

* Corresponding author. Mailing address: Washington University School of Medicine, Department of Pathology & Immunology, Campus Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110-1093. Phone: (314) 747-6547. Fax: (314) 362-8888. E-mail: fremont{at}wustl.edu.

{triangledown} Published ahead of print on 20 September 2006.

Journal of Virology, December 2006, p. 11467-11474, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01125-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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