Solution X-ray scattering studies of DENV-4 NS2B18NS3. (a) SAXS pattern (circles) of DENV-4 NS2B18NS3 at concentrations of 1.5 mg ml−1 (brown), 2.8 mg ml−1 (orange) and 5.4 mg ml−1 (blue). Inset: Guinier plots show linearity at all concentrations used, indicating no aggregation (Supplementary Fig. S3a). A slight concentration dependency was observed at the highest concentration (5.4 mg ml−1; Supplementary Fig. S2a). Therefore, the SAXS patterns of DENV-4 NS2B18NS3 at 1.5 and 2.8 mg ml−1 were merged to improve the data quality. The scattering profiles are offset for clarity by applying arbitrary scale factors. (b) Small-angle X-ray scattering pattern (black circles) and calculated scattering profiles from crystal structures (red line, PDB entry 2vbc; green line, PDB entry 2wzq; blue line, PDB entry 2whx) of DENV-4 NS2B18NS3. (c) Overlapping of the pair-distance distribution functions P(r) of NS2B18NS3 of DENV-2 (red line) and DENV-4 (blue line) shows no difference between the two serotypes. (d) Normalized Kratky plot of DENV-2 NS2B18NS3 (red dots) compared with the DENV-4 NS2B18NS3 protein (blue dots) and the compact globular lysozyme (grey dots) with a peak (grey dotted line) representing the theoretical peak and assuming an ideal Guinier region of a globular particle. The scattering pattern of DENV-4 and DENV-2 NS3 exhibits a broad bell-shaped profile shifted towards the right with respect to standard globular proteins, indicating the presence of motion in the protein. (e) Porod–Debye plots (blue circles, DENV-4 NS2B18NS3; red circles, DENV-2 NS2B18NS3) and their fit lines. The absence of a Porod–Debye plateau in the plot suggests that DENV-4 NS2B18NS3 (Porod exponent = 3.5) and DENV-2 NS2B18NS3 (Porod exponent = 3.5) are flexible in solution. (f) Ab initio
DAMMIF envelopes superimposed onto a cartoon representation of the crystallographic structure of DENV-4 NS2B18NS3 (PDB entry 2vbc), with the protease coloured blue and the helicase coloured orange. Front (left), side (middle) and bottom (right) views are displayed.