Fig. 7: Schematic representation of the mechanism of heme-mediated inhibition of α-Syn fibrillation.

a The fibrillation of α-Syn^54,79 proceeds through the formation of an on-pathway (fibril-forming) fundamental protofilament kernel¹⁰ which contains the β sheet Greek-key motif⁹ (also termed as a bent β-arch structure) and serves as a ‘building block’ for fibrillation. b Fibril formation occurs via stacking of these kernels into protofilaments which subsequently interlace at the steric zipper interface¹⁰ to form mature fibrils. c Addition of heme at an initial stage stabilizes it into a twisted form (oligomer₁) which does not form fibrillar structures. d Addition of heme at a later stage (when fibrillation has already initiated) causes disassembly of α-Syn oligomers/fibrils by inducing a twist/ distortion in the fundamental kernels resulting in a twisted Greek-key structural fold (oligomer₂).