Crystal structure of dengue virus type 1 envelope protein in the postfusion conformation and its implications for membrane fusion.
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.
Nayak
Vinod
V
Department of Molecular Biophysics & Biochemistry, The Bass Center for Structural Biology, Yale University, New Haven, Connecticut 06520, USA.
Dessau
Moshe
M
Kucera
Kaury
K
Anthony
Karen
K
Ledizet
Michel
M
Modis
Yorgo
Y
D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D003716:Dengue Virus / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D008561:Membrane Fusion; D008958:Models, Molecular; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization
D014759:Viral Envelope Proteins