Fig. 7. Phage-displayed antibody fragments differentially binding wild-type PrPC, but not PrP2Cys, confer neuroprotection.
a, Preferential binding of the selected Fabs to rmPrP23–231 over rmPrP2Cys. With the exception of FabE2, the Fabs show higher apparent affinity for rmPrP23–231 than rmPrP2Cys. One datapoint corresponds to the mean ± s.e.m. of two technical replicates. The experiment was repeated twice. b, FabA10 and FabD9 conferred neuroprotection in prion-infected tga20 COCS. c, Quantification of NeuN fluorescence intensity from b, expressed as percentage of untreated (–) NBH. Scale bar: 500 µm. One datapoint corresponds to an independent, organotypic cultured slice. Two-way ANOVA with Dunnett’s multiple comparison test, P values are adjusted for multiple testing: RML untreated (–) versus RML A10: P = 0.006, RML untreated (–) versus RML D9: P = 0.009, **P < 0.01, n.s.: not significant, P > 0.05. d, Structure of PrPC (white) in complex with FabA10 (violet) obtained by NMR-validated docking and MD. mPrP90–231 residues whose NMR signal is affected by FabA10 binding are colored blue; residues with no NMR information are gray; residues mutated to Cys are yellow. e, There is partial overlap (green) between the epitopes of POM1 (red) and FabA10 (blue). The 2Cys are in yellow. PrPC is depicted in different orientations in d and e.