Crystal structure of dengue virus type 1 envelope protein in the postfusion conformation and its implications for membrane fusion

Vinod Nayak, Moshe Dessau, Kaury Kucera, Karen Anthony, Michel Ledizet, Yorgo Modis

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4338-4344
Number of pages7
JournalJournal of Virology
Volume83
Issue number9
DOIs
StatePublished - May 2009
Externally publishedYes

Fingerprint

Dive into the research topics of 'Crystal structure of dengue virus type 1 envelope protein in the postfusion conformation and its implications for membrane fusion'. Together they form a unique fingerprint.

Cite this