Extended Data Fig. 9: Point mutations at binder–target interfaces disrupt binding, while the designs inhibit Amylin fibril formation and dissociate existing fibrils.
From: Diffusing protein binders to intrinsically disordered proteins
a-c, Designed complex structures of binders (light pink) in complex with their respective IDP targets (slate) amylin (a, binder Amy36 as representative), C-peptide (b), and VP48 (c). Point mutations introduced at the predicted interface are highlighted with arrows and dashed circles: L12T and L16T for amylin; L26T and L30T for C-peptide; and M10K and L24T for VP48. d, Amylin binders Amylin-22αβL and Amylin-36αβ inhibit fibril formation in a concentration-dependent manner. The initial concentration of Amylin monomer was 10 μM, with subsequent additions of binders at 2.5 μM, 0.25 μM, and 0.025 μM, establishing molar ratios of binder to Amylin of 1:4, 1:40, and 1:400, respectively. e,f, Negative stain electron microscopy images were taken of 40 μM Amylin monomer samples following the addition of 10 μM Amylin-36αβ (e) and Amylin-22αβL (f) at 1 h and 18 h, respectively. Scale bars, 100 nm.
