PMC

Dengue virus NS1 variable regions (red), identified from an alignment of consensus sequences from the four major dengue serotypes, mapped onto dimer surface.

NS1 hexamer. (A,B) Orthogonal views of crystallographic NS1 hexamer (cartoon – dimers in blue, yellow and green) superposed on cryo-EM map from []. Wing domains (in red circles) are not accounted for in cryo-EM map. (C) Outer surface of NS1 hexamer decorated with sulfate-binding, antibody-binding and glycosylation sites. Blue dimer from A and B is shown in grey. Glycosylation (black, red spheres) and sulfate sites (yellow circles) are indicated. Epitope for the neutralizing Fab 22NS1 is shown in orange.

NS1 dimer structure. (A) NS1 dimer with “inner face” towards viewer. Blue: β-roll, yellow: RIG-I like wing domain, and red: β-ladder. (B) Dissection of NS1 structure highlighting three domains. (left) β-roll and connector subdomain (orange), (center) β-ladder with “spaghetti” loop (pale salmon), and (right) wing domain with connector subdomain. (C) NS1 dimer surface (colored as in A) with inner face placed on membrane (green). Hydrophobic protrusion, including residues that affect virus RNA replication (10 – 11 and 159 – 162), interacts with the membrane surface. Sugar residues decorate the outer surface (white, red and blue spheres).