<p>The flavivirus E protein contains three distinct domains (DI–III) and forms antiparallel dimers on the mature virus particle. Shown is the crystal structure of the soluble ectodomain of the DENV2 E protein dimer (PDB 1OAN) as viewed from the top (top panels) and side (bottom panels). (<b>A</b>) Ribbon diagram of the E protein with DI, II, and III colored in red, yellow, and blue, respectively <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003761#ppat.1003761-Modis1" target="_blank">[102]</a>. (<b>B</b>) The 130 amino acid residues in the soluble ectodomain that differ between the DENV1 and DENV2 components of the NIAID candidate tetravalent vaccine are highlighted in blue on one E protein; the second E protein of the dimer is shaded in green. (<b>C</b>) Surface accessibility was estimated using solvent accessible surface areas of the residues determined from the crystal structure (UCSF Chimera package), with a cut-off value of 30 Å<sup>2 </sup><a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003761#ppat.1003761-Huang1" target="_blank">[103]</a>. Residues selected for study were restricted to the top of the dimer. The 68 residues identified as surface-accessible differences between DENV1 WP and DENV2 NGC are shown in red.</p
