Fig. 5: Cryo-EM structure of the wt PV2-CP17 complex.

a Three-dimensional reconstruction of wt PV2 VLP after incubation with a molar excess of the benzene sulphonamide CP17. The VLP is viewed along the icosahedral twofold symmetry axis and coloured by radial distance in Å from the particle centre according to the colour key provided. Cryo-EM electron potential features for CP17 are coloured cyan. A single kite-shaped capsid protomer is outlined in white and five, three and twofold symmetry axes labelled with symbols. b View looking down the icosahedral fivefold symmetry axis, coloured as in a showing CP17 bound at the interprotomer interface. c CP17 shown in close-up as a cyan stick model fitted into the cryo-EM electron potential map, with elemental colouring for oxygen (red), nitrogen (blue) and sulfur (yellow). The map is displayed at a contour level of 1.0 σ and rendered at a radius of 2 Å around atoms. d Cartoon representation of CP17 (cyan stick model) bound in the VP1–VP3 interprotomer surface pocket between neighbouring capsid protomers. VP1 and VP3 of protomer A are coloured blue and red, respectively, and VP1 of protomer B is coloured grey. Amino acid side chains for residues of VP1 and VP3 forming the CP17 binding pocket are shown as sticks and labelled. Hydrogen bond and salt–bridge interactions are shown as green dashes and distances labelled. The sphingosine lipid modelled into the VP1 subunit hydrophobic pocket is shown as an orange stick model. e Ligplot+⁶¹ representation of the CP17 binding pocket showing details of key interactions. Hydrogen bonds and salt-bridges are shown as green dashes with distances labelled, and hydrophobic interactions as red arcs. f Superposition of the CP17 binding sites between wt PV2 VLP and CVB3²⁹. VP1, VP3 and CP17 of wt PV2-CP17 are coloured as in d, and the CVB3 pocket and CP17 are coloured pale gold. Side chains interacting with CP17 from wt PV2 and CVB3 are labelled and colour coded. g Semi-transparent surface representation of the wt PV2-CP17 pocket coloured by hydrophobicity from dark cyan (hydrophilic) to dark gold (hydrophobic). CP17 is shown as cyan sticks and residues of note (see Discussion) are labelled.