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Journal of Virology, May 2009, p. 4338-4344, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02574-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Crystal Structure of Dengue Virus Type 1 Envelope Protein in the Postfusion Conformation and Its Implications for Membrane Fusion {triangledown}

Vinod Nayak,1,{dagger} Moshe Dessau,1 Kaury Kucera,1 Karen Anthony,2 Michel Ledizet,2 and Yorgo Modis1*

Department of Molecular Biophysics & Biochemistry, The Bass Center for Structural Biology, Yale University, 266 Whitney Ave., New Haven, Connecticut 06520,1 L2 Diagnostics, 300 George St., New Haven, Connecticut 065112

Received 13 December 2008/ Accepted 11 February 2009

Dengue virus relies on a conformational change in its envelope protein, E, to fuse the viral lipid membrane with the endosomal membrane and thereby deliver the viral genome into the cytosol. We have determined the crystal structure of a soluble fragment E (sE) of dengue virus type 1 (DEN-1). The protein is in the postfusion conformation even though it was not exposed to a lipid membrane or detergent. At the domain I-domain III interface, 4 polar residues form a tight cluster that is absent in other flaviviral postfusion structures. Two of these residues, His-282 and His-317, are conserved in flaviviruses and are part of the "pH sensor" that triggers the fusogenic conformational change in E, at the reduced pH of the endosome. In the fusion loop, Phe-108 adopts a distinct conformation, forming additional trimer contacts and filling the bowl-shaped concavity observed at the tip of the DEN-2 sE trimer.

* Corresponding author. Mailing address: 266 Whitney Ave., Bass 430, New Haven, CT 06520. Phone: (203) 432-4330. Fax: (203) 432-1296. E-mail: yorgo.modis{at}yale.edu

{triangledown} Published ahead of print on 25 February 2009.

{dagger} Present address: The Scripps Research Institute Florida, 5353 Parkside Drive, Jupiter, FL 33458.

Journal of Virology, May 2009, p. 4338-4344, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02574-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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