Fig. 7: Comparison of non-neutralizing antibodies targeting E2.

a Crystal structures of 2A12–E2 (4WEB), E1–E2 (6WO5), and HEPC46–E2 (6MEJ) complexes and cryo-EM structure of CBH7–E2 complex. E1 is a non-neutralizing antibody, not the E1 envelope glycoprotein. The structures are superposed on E2 of the CBH4B–E2 complex to illustrate differences in the orientation of the non-neutralizing antibodies with respect to E2. b Axes of angles of approach of E1 (salmon), 2A12 (green), HEPC46 (maroon), and CBH4B (cyan) over E2 (blue). c Electrostatic surface potential map of E2 in the CBH4B–E2 and 2A12–E2 complexes shows that the V_HCDR loops of 2A12 only interact with the back layer, whereas the V_HCDR loops of CBH4B also contact pVR3. The back layer and pVR3 regions are outlined with black dashes. The electropositive patch on the back layer of E2 is labeled. V_HCDR1, V_HCDR2, and V_HCDR3 are colored red, green, and blue, respectively. d Surface representation of E2 (magenta) in the HEPC46–E2 and E1–E2 complexes shows positioning of V_HCDR loops. In E1, V_HCDR1 contacts the CD81 binding loop (light blue), and V_HCDR3 interacts with β-sandwich turn T542–N548 (orange), while in HEPC46, all V_HCDRs anchor this β-sandwich turn. V_HCDR1, V_HCDR2, and V_HCDR3 are colored red, green, and blue, respectively. e The tips of the V_HCDR2 loops of E1 (salmon) and HEPC46 (maroon) interact with the same hydrophobic patch on E2 formed by β-sandwich residues P513–V516.