Fig. 9: A conserved binding site in flaviviruses for lipid pocket factors.
a, b Zooms of the lipid-binding sites in bDENV-2. The E protein (cartoon/sticks) is coloured by conservation from high (magenta) to low (cyan) based on an alignment of mammalian flaviviruses (Supplementary Table 4). The sequence conservation is displayed as sequence logos where amino acids at each position are listed as stacked single letter codes in a font size proportional to the frequency of occurrence. The stem helices are shown as cylinders and contact residues between E and the lipids highlighted by red asterisks. c Replication of viruses containing site-specific mutants was analysed at passage 1 by immunoplaque assay, recovery was only observed for mutant F422A. The open circles represent individual data point and bar graphs represent the mean value from two independent viral titrations. d Comparison of the TM, stem and ectodomain (EDI–III) of E before/after maturation across the viral membrane (left) and from the outside of the particle (right). The membrane domain is display in a cartoon with H1 (yellow), H2–H3 (orange) and the transmembrane helices (purple) labelled accordingly. For the mature structure, the lipid molecules are represented as sticks within a surface representation of the surrounding density from the reconstruction of mature bDENV-2. For the immature structure, the sequence of DENV-2 was mapped onto a previously deposited c-alpha model (PDB: 4B03) in Coot and used to generate a cartoon representation. Arrows indicate the positions of the pocket factors in the mature form. They do not represent the actual movement of lipids as their location in the immature state is unknown.
