A ligand-binding pocket in the dengue virus envelope glycoprotein.
Dengue virus is an emerging global health threat. Its major envelope glycoprotein, E, mediates viral attachment and entry by membrane fusion. A crystal structure of the soluble ectodomain of E from dengue virus type 2 reveals a hydrophobic pocket lined by residues that influence the pH threshold for fusion. The pocket, which accepts a hydrophobic ligand, opens and closes through a conformational shift in a beta-hairpin at the interface between two domains. These features point to a structural pathway for the fusion-activating transition and suggest a strategy for finding small-molecule inhibitors of dengue and other flaviviruses.
Modis
Yorgo
Y
Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, 320 Longwood Avenue, Boston, MA 02115, USA.
Ogata
Steven
S
Clements
David
D
Harrison
Stephen C
SC
D001665:Binding Sites; D018360:Crystallography, X-Ray; D003716:Dengue Virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity / Q000502:physiology; D019281:Dimerization; D006801:Humans; D008024:Ligands; D008561:Membrane Fusion; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
C051821:E-glycoprotein, Dengue virus type 2; D008024:Ligands; D010446:Peptide Fragments; D021122:Protein Subunits; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins