Supplementary Figure 1: Structural modeling of potential interactions between ADI-15946 and the glycan cap. | Nature Structural & Molecular Biology

Supplementary Figure 1: Structural modeling of potential interactions between ADI-15946 and the glycan cap.

From: Structural basis of broad ebolavirus neutralization by a human survivor antibody

Supplementary Figure 1

(a) The structure of uncleaved GP (PDB 5JQ3) showing the position of the β17-β18 loop bound to the 310 pocket. The connecting residues between the bound peptide and the β-sheets are unresolved in this structure and are indicated here as dotted lines. GP1 is shown in teal, GP2 in light cyan, and the glycan cap is shown in light green. (b) Structural alignment of uncleaved GP to the EBOV GPCL–ADI-15946 complex shows that the mAb might make favorable interactions with the glycan cap even though binding displaces the glycan cap β17-β18 loop from the 310 pocket (arrow showing displacement of loop). The heavy and light chains of ADI-15946 are colored dark orange and light orange respectively. (c) The heavy and light chain of ADI-15946 may form favorable interactions with the glycan cap. For example, HC R100G and LC Y92 are oriented such that they could potentially form hydrogen bonds with the 100% conserved GP1 residue, Q251. (d) Cathepsin access to the β13-β14 loop, shown as a green cartoon with the unresolved continuation of the loop as a dotted line, is likely inhibited by the steric bulk of ADI-15946 upon binding to GP. The structural alignment shows that the β13-β14 loop passes within close proximity to ADI-15946 and highlights a possible interaction between GP1 residue S211 and ADI-15946 LC residues F67 and D70.