Fig. 2: The K510E escape mutation probably clashes with ADI-15946 CDR H3. | Nature Structural & Molecular Biology

Fig. 2: The K510E escape mutation probably clashes with ADI-15946 CDR H3.

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

Fig. 2

a, Stereoview of the EBOV GPCL–ADI-15946 complex (left; ADI-15946 in orange, and GPCL in dark and light teal for GP1 and GP2, respectively) and electrostatic surface potential (right; color scale shown in c) showing that residue K510 of GP2 binds into a negatively charged pocket created by ADI-15946 CDR H3. b, Similar views to a, with modeling of an escape mutant of ADI-15946, GP K510E, suggesting that K510E clashes with CDR H3 and introduces conflicting negative charge into the CDR H3 pocket. c, Open-book representation of EBOV GPCL and ADI-15946 showing electrostatic surface potential colored according to included scale. GPCL is shown on the left with the epitope outlined in black. ADI-15946 is shown on the right with the paratope outlined in black. kb, Boltzmann’s constant (1.3806504 × 10–23 J K–1). T, temperature (310 ºK). ec, charge of an electron (1.60217646 × 10–19 C). d, Binding and neutralization assays showing the capacity of ADI-15946 variants containing either the D100CA or the L100FA mutation to bind to rVSV-BDBV GP (wild type, WT or K510E) in an ELISA (top, mean ± s.d., n = 4 biologically independent samples) and neutralize infection by these viruses (bottom, mean ± s.d., n = 6 biologically independent samples). Electrostatic surface potentials in a and c were generated using the APBS plugin with Pymol. A450 nm, absorbance at 450 nm.