Extended Data Fig. 7: Alphafold predictions of unresolved or CD81 binding regions, epitope characterization, and epitope clash analysis on the E1/E2 homodimeric complex.
From: The hepatitis C virus envelope protein complex is a dimer of heterodimers
a, A comparison between selected residues (HVR1 + AS412: 384–423, E2-FL: 422–460, CD81bl: 519–535; in the case of the CD81bl, additional backbone residues are shown in white as these were used to correctly orient the CD81bl structures) of our modeled E2 structure and the AlphaFold predicted structure. b, Key epitopes targeted by cross-reactive antibodies are highlighted on the soluble part of the E1/E2 homodimeric complex (8rk0). The glycan density is depicted in dark grey. The epitope of AR3A is partly flexible in our complex, likely due to not having Fabs bound. The epitopes of IGH505, HCV1, AR3A, and AR4A have been directly visualized in solved structures, whereas those of AR2A and AR5A are defined indirectly through alanine scanning. (c-e) Structure of Fabs bound to E2 (c: 6bkb, d: 7t6x, e: 4dgv) superimposed on the on the soluble part of E1/E2 homodimer structure (8rk0). E1 is depicted in steel blue, E2 in green, HVR1 in purple, AS412 in blue and Fabs in yellow. In panel d, only the variable domain of the light chain and the heavy chain is displayed. Zoom-ins depict the clash of the AR4A heavy chain with HVR1 in red (d) or the HCV1 heavy chain with E2-FL in green (e). Unresolved regions are indicated by broken lines.
