Fig. 5: Cryo-EM structures of CVA6 particles in complex with 1F4 Fab.

a, b Cryo-EM density maps of CVA6-HeB-1F4 in two conformations: 1F4-bound virion (a) and empty particle (b). Both maps are radially colored and viewed along the twofold axis. An icosahedral asymmetric unit is marked by a black triangle. 2D classification resolved 98.9% 1F4-bound virions and 1.1% empty particles. c, d Density maps of twofold-related protomers in the 1F4-bound virion (c) and empty particle (d), superimposed with atomic models. Conformational differences are outlined by yellow dashed rectangles. 1F4 Fab is omitted in (c) for clarity. e, f Atomic models of the VP1 hydrophobic pocket in the 1F4-bound virion (e) and empty particle (f). The pocket factor (magenta) is present in the 1F4-bound virion but absent in empty particle. Consequently, the VP1 pocket collapses in empty particle, accompanied by a significant inward shift of the VP1 GH loop (residues 223–225; red arrowhead, RMSD = 1.4 Å). 1F4 Fab is omitted in (e) for clarity. The five-fold axis is indicated. g, h Central cross-sections of the 1F4-bound virion (g) and empty particle (h) along the z-axis. Black arrows indicate 1F4 Fab density. Central sections are displayed without masking or sharpening to preserve the native density information. i Atomic model of a CVA6 protomer bound to 1F4 Fab. VH is cyan and VL is magenta. The five-fold axis is indicated. j Enlarged views of CVA6–1F4 interaction interfaces. Hydrogen bonds are marked with gray dashed lines. k Surface footprint of 1F4 variable domains on the CVA6 virion using RIVEM analysis. Contour lines denote KRM1 (orange), 1F4 VL (white), and 1F4 VH (yellow). l The CVA6–1F4 complex structure was superimposed onto the CVA6–KRM1 complex, revealing spatial clashes between the 1F4 VL domain (magenta) and KRM1 (tomato). Protomer 1 is colored pink; Protomer 2 is colored white.