Figure 5.

F56 and W60 in mβ₂m Form Interactions Required for Amyloid Inhibition

(A) The lowest-energy calculated structure of the ΔN6 (red)-mβ₂m (green) complex highlighting F56 and W60 in the interface. Interface residues are colored blue on ΔΝ6 (right).

(B) Representative sample resonances in the ¹H-¹⁵N HSQC spectrum of ¹⁵N-labeled ΔΝ6 (80 μM; red) that show chemical shift changes upon the addition of ¹⁴N-labeled mβ₂m (green) but not its F56E/W60E variant (160 μM; blue). Addition of mβ₂m shifts the resonances of ΔΝ6 toward their positions at pH 8.2 (black), where ΔN6 is not amyloidogenic (Eichner et al., 2011) (additional examples are shown in Figure S5A).

(C) Fibrillation kinetics of ΔΝ6 alone (20 μΜ; pink) at pH 6.2 and in the presence of a 2-fold molar excess of mβ₂m (green) or F56E/W60E mβ₂m (blue).

(D) Sedimentation velocity AUC traces of ΔΝ6 alone (60 μM; red), ΔΝ6 (60 μM) mixed with an equimolar concentration of mβ₂m (green), or F56E/W60E mβ₂m (blue).