Figure 5. Structure of inter-dimer-epitope antibodies rhMZ119-D and rhMZ104-D in complex with ZIKV E glycoprotein.

(A) Left: top view of the co-crystal structure of rhMZ119-D in complex with ZIKV E (PRABC59). rhMZ119-D Fab heavy and light chains are shown in surface representation and are colored wheat and yellow, respectively, while two ZIKV E protomers are shown in ribbon representation, colored blue and gray. ZIKV E protomers, left to right, are labeled as I and II. Right: 2Fo-Fc electron density for the rhMZ119-D and ZIKV E interface residues is shown as gray mesh (contoured at 1.5σ).

(B) Epitope footprint of rhMZ119-D antibody is shown as solid yellow colored line, displayed on two ZIKV E protomers in surface representation.

(C) Left: top view of the crystal structure of rhMZ104-D in complex with ZIKV E (PRABC59). rhMZ104-D Fab heavy and light chains are shown in surface representation and are colored with dark and light orange, respectively, while two ZIKV E protomers are shown in ribbon representation and colored blue and gray. ZIKV E protomers, left to right, are labeled as I and II. Right: 2Fo-Fc electron density for the rhMZ104-D and ZIKV E interface residues is shown as gray mesh (contoured at 1.5σ).

(D) Epitope footprint of rhMZ104-D antibody is shown as solid orange colored line, displayed on two ZIKV E protomers in surface representation.

(E) rhMZ119-D contact residues are shown as sticks based on (1) CDRs L1, L2, and L3; (2) CDR FRL3; and (3) CDR H1, H2, and H3 antibody-contacting regions. ZIKV E contact residues of protomer II are marked with prime (′); b strand residues 63–73 on protomer I are highlighted in dark blue color. SHM residues are highlighted in bright red color.

(F) rhMZ104-D contact residues are shown as sticks based on (1) CDRs L1, L2, and L3; (2) CDR H3 antibody-contacting regions; b strand residues 63–73 on protomer I are highlighted in dark blue color.

(G) Antibodies rhMZ119-D and rhMZ104-D are superimposed on ZIKV E protomer I. Both antibodies approach the E dimer at an angle of 90° with respect to each other.

(H) Epitopes for rhMZ104-D, rhMZ119-D, and ZIKV-195 antibodies are represented with orange, yellow, and cyan colored lines, respectively. rhMZ104-D andZIKV-195 (PDB: 6MID) antibodies were overlaid onto the rhMZ119-D ZIKV E structure to map the epitopes.

(I) Group D antibodies were assessed for binding using shotgun mutagenesis epitope mapping. Alanine or serine mutations, which dramatically affected group D antibody binding, are shown in sphere representation on the ZIKV E structure and indicated on the right. Residues important for binding for all group D mAbs are highlighted in orange.

See also Figures S3–S5 and Tables S4 and S5.