Supplementary Figure 2: Conformational changes influence binding of ADI-15946. | Nature Structural & Molecular Biology

Supplementary Figure 2: Conformational changes influence binding of ADI-15946.

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

Supplementary Figure 2

(a) Cartoon illustration of GP with mucin-like domains (MLD) and glycan cap domains (CAP) illustrated as green ovals. The β17-β18 loop of the glycan cap descends to cover the ADI-15946 epitope (orange). This loop may exist in a dynamic equilibrium between ‘tethered’ and ‘loose’ positions that mask and expose the ADI-15946 epitope. (b) The W291R point mutation in the β17-β18 loop results in enhanced exposure of the ADI-15946 epitope. (c) Antibody FVM09 (gray) which binds to the β17-β18 loop appears to lift it up and away30, also better exposing the ADI-15946 epitope. (d) Enzymatic cleavage of GP deletes the glycan cap and the β17-β18 loop, better exposing the ADI-15946 epitope. Deletion of the glycan cap and β17-β18 loop enhances neutralization by ~100-fold. Mutation of the loop and binding of the loop by FVM09 enhance ADI-15946 neutralization by ~10- and 15-fold, respectively.