Extended Data Fig. 8: Characterization of the CD81 binding site.

Interaction regions and critical contact residues between CD81 and E2. a, The E1/E2 homodimer (8rjj) and the E2-CD81 complex (7mwx) were superimposed and are shown side by side in these aligned front and top views. Residues forming the CD81-E2 interface²⁰ are highlighted on both the homodimeric E1/E2 complex (left, 8rjj) and the E2 structure bound to CD81 (right, 7mwx) and color-coded as detailed in the legend. In 8rjj, one E1/E2 heterodimer is represented in gray and the other in light gray. In 7mwx, E2 is represented in gray. b, A close-up view on the part of AS412/E2-FL (top panel, blue) and the CD81bl (lower panel, yellow) adopting different conformations, with residues critical for CD81 binding and virus entry highlighted^49,50. c, A comparison between the aligned residues (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 structures elucidated through Fab-based methods. E2 structures with E2-FL in conformation A (4mwf, 6mei, 6uyg, 6meh, 6mej, 7t6x) and conformation B (6wo5)¹⁸. E2 structures with CD81bl in retracted (7mww) and bent (8dk6) conformation. Unresolved regions are indicated by broken lines.