A human monoclonal antibody binds within the poliovirus receptor-binding site to neutralize all three serotypes

Figures

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  Fig. 1. 9H2 Fab binds virus with the same mode of binding in all three serotypes. A Surface rendered DeepEMhancer sharpened maps are colored according to radius (color key) and show density corresponding to the 9H2 Fab. B The central section shows the Fab has a similar magnitude of density as the capsid. C FSC curves indicate resolution ranging from 2.7–3.1 Å at the gold standard 0.143 cutoff. D Refined models of single virus protomer (VP1–4; blue, green, red, yellow) and bound 9H2 variable domain (heavy and light chain; dark and light gray). Live virus 1, 2, and 3 data were taken at magnification x59,000, x59,000, and x120,000 resulting in pixel sizes of 1.1, 1.1, and 1.2, respectively. E For each complex, a representative area illustrating the quality of the model built into the map is shown. The map area highlighted includes residues VP1 270–273 and VP2 192–194. Coloration is VP1 (blue) and VP2 (green) with additional coloring by heteroatom.

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  Fig. 2. Local resolution maps. Local resolution values were measured in Angstroms and displayed with a surface rendered map for each live virus-Fab complex. The best resolution is present in the capsid shell while the poorest is found in the hinge region of the Fab fragments.

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  Fig. 3. A Mesa Loop is Flexible in WTPV2 and SPV3. VP1 residues 96 to 103 are disordered in the WTPV2 and SPV3 complexes in contrast to the inactivated complexes of the same serotype. Residues identified as contacts are displayed as spheres matching their chain color (heavy and light chain; dark and light gray; VP1; blue).

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  Fig. 4. 9H2 model contacts. View is looking down tangent to the canyon at individual 9H2-poliovirus complex protomer models. Residues identified as contacts are displayed as spheres matching their chain color (heavy and light chain; dark and light gray; VP1–4; blue, green, red, yellow; palmitic acid as a pocket factor, orange).

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  Fig. 5. 9H2 footprint roadmaps. Road maps of the virus surface are represented as a quilt of amino acids, shown as a projection with the icosahedral asymmetric unit indicated by the triangular boundary58. Residues for live (left) and inactive virus (right) comprising the footprint of Fab 9H2 are colored according to the serotype of poliovirus in complex: red, serotype 1; gold, serotype 2; blue, serotype 3.

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  Fig. 6. Antigenic sites, PVR footprint, and 9H2 summary footprint. Amino acids are numbered as sequence-equivalent residues in an alignment to WTPV1. A Antigenic sites (rodent models) as summarized by Fiore et al. 199723; blue, N-Ag I; red, N-Ag II; yellow, N-Ag III. The 9H2 footprint has 5 non-universal contact residues that overlap with N-Ag I & II. B The footprint of the PV receptor CD155 (cyan)15 has a significant overlap with the 9H2 footprint. C Summary footprint of 9H2. Blue, universal contacts in all 9H2 complexes (VP1 T88, I89, A106, V107, W108, D114, E168, L228; VP3 A235); red, non-universal contacts. The canyon (black) and CD 155 footprint (cyan) are indicated. D Roadmap has been colored by radius from the center of the virus. Color key in Å.