Crystal structure of E106 Fab in complex with DENV-1 E DIII.

<p>(<b>A</b>) The E106 Fab epitope on DENV-1 E DIII is comprised of residues in the A-strand (K307 and K310), the end of the B-strand (K325 and Y326), and the connecting BC (E327, T329, and D330) and DE (K361 and E362) loops. The immunoglobulin-like DIII is shown in blue (epitope regions in magenta), with the E106 heavy chain in green and light chain in cyan. (<b>B</b>) Heavy chain residue W98 binds in a deep pocket contributed by the aliphatic groups of side chain DENV-1 E DIII residues K307, K325, and E327 and main chain of Y326, in stereo (top panel). The electron density map is contoured at 1.1σ. Ball and stick representation of the molecular interactions involving T329 (the residue that escapes neutralization <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004072#ppat.1004072-Shrestha1" target="_blank">[13]</a> in stereo (bottom panel). (<b>C</b>) Surface representation of DENV-1 E DIII (top) and E106 Fab (bottom) highlighting residues making direct contacts in the complex (see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004072#ppat.1004072.s001" target="_blank">Table S1</a>). DENV-1 E DIII residues previously identified by yeast surface display are displayed in magenta <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004072#ppat.1004072-Shrestha1" target="_blank">[13]</a>. (<b>D</b>) The structural epitope on DENV-1 DIII is shown in ribbon representation. (<b>E</b>) Sequence of DIII of DENV-1 aligned with that of DENV-2, -3, -4 and WNV highlighting the E106 structural epitope, which is conserved in DENV-1 genotypes but not DENV serotypes or WNV. Identical residues are represented by a dot, deleted residues by a hash. For comparison, The DIII structural epitopes of WNV E16, DENV-2 1A1D-2, DENV cross-reactive 4E11 and 2H12 MAbs and DENV-1-E111 contact residues are labeled with green, purple, light purple, orange and cyan asterisks respectively <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004072#ppat.1004072-Cockburn1" target="_blank">[10]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004072#ppat.1004072-Midgley1" target="_blank">[17]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004072#ppat.1004072-Nybakken1" target="_blank">[20]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004072#ppat.1004072-Lok1" target="_blank">[21]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004072#ppat.1004072-Austin1" target="_blank">[33]</a>.