Figure 4. Characteristics of WT and G14R aSyn filaments.

(A) TEM micrograph of wild-type (WT) aSyn amyloid filaments. Black arrows mark select filament ends. Scale bar: 100 nm. (B) TEM micrograph of G14R aSyn amyloid filaments. In the micrograph multiple aggregates consisting of laterally associated filaments can be seen. Black arrows indicate filament ends of exemplary filaments that were used for SPA processing. Scale bar: 100 nm. (C) 2D class averages (706 Å box size) of twisting WT aSyn fibrils, showing an interaction between two protofilaments. (D) 2D class averages (706 Å box size) of twisting WT aSyn filaments, showing interaction between two protofilaments (2PF) or a single protofilament (1PF). Scale bar: 50 nm. (E) Overview of the electron density map of WT aSyn filaments. (F) Overview of the electron density map of G14R aSyn filaments. (G) Amino acid sequence of human aSyn with distinct regions color-coded (N-Terminus in orange, middle hydrophobic region in purple, and C-Terminus in green). Scale bar: 50 nm. (H) The electron density map together with the atomic model of WT aSyn amyloid filaments featuring a single beta-sheet layer formed by two interacting protofilaments. The protofilament interface is stabilized by a K45-E57 salt bridge. (I) The electron density map together with the atomic model of a single beta-sheet of G14R aSyn amyloid filaments. The mutated residue is indicated in red, while residues forming the salt-bridge in the WT are marked in green.