Figure 3: bADDLs avidly bind PrP in a manner that can be blocked by certain anti-PrP antibodies. | Nature Communications

Figure 3: bADDLs avidly bind PrP in a manner that can be blocked by certain anti-PrP antibodies.

From: Interaction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites

Figure 3

(a) Dose response curves of ADDLs (green) and bADDLs (red) to plate-bound full-length PrP or background wells coated with BSA (light green and red for ADDLs and bADDLs, respectively). (b) Binding of 100 nM bADDLs to huPrP23−231, huPrP91−231 and huPrP119−231. (c) Competition of binding of bADDLs to surface-bound huPrP23−231 by different constructs of PrP. (d) Inhibition of bADDL binding to huPrP23−231 by ICSM-35 after pre-incubation of surface-bound huPrP23−231 with ICSM-35. (e) Screen of the ICSM panel of antibodies using a high throughput DELFIA to detect bADDL or antibody binding. Antibodies are classed in different binding regions 95–105 (red), 131–153 (yellow), structured region (magenta) or undefined epitopes (blue). ICSM-18 and ICSM-35 are highlighted. Surface-bound huPrP23−231 was pre-incubated for 1 h with 100 nM antibodies and then incubated for 1 h with or without 100 nM bADDLs before detection with either Eu-N1 streptavidin or Eu-N1 anti-mouse antibody. (f, g) Model of the PrP/ICSM-18 complex (f) based on the published crystal structure and with the antibody extension built in with PrP and the ICSM-18 epitope (yellow) highlighted; (g) Modelled structure of the PrP/Aβ interaction with Aβ spheroids (green), PrP (magenta), the ICSM-18 epitope (yellow) and the unstructured ICSM-35 epitope (red) built in, highlighting the large distance between Aβ-binding site and the ICSM-18 epitope. All graphs show mean±s.d. and are an average of at least three data points.

Back to article page