Extended Data Fig. 2: Cryo-EM structure of TMEM106B and Aβ42 filaments from the prefrontal cortex of FTLD-FET individual 4.

a-c, Cryo-EM reference-free 2D class averages of the filament segments used to reconstruct TMEM106B singlet (a), TMEM106B doublet (b), and Aβ42 (c) filaments from FTLD-FET individual 4. Scale bars, 10 nm. d-f, Cryo-EM reconstructions of TMEM106B singlet (d), TMEM106B doublet (e), and Aβ42 (f) filaments, viewed as central slices perpendicular to the helical axis. Scale bar, 2 nm. Resolution estimates are indicated. g, Fit of the published atomic model of singlet TMEM106B type 1 filaments (PDB- ID: 7QVC) into the density map (grey mesh), shown for a single peptide perpendicular to the helical axis. h, Fit of the published atomic model of doublet TMEM106B type 1 filaments (PDB-ID: 7QVF) into the density map (grey mesh), shown for two C2 symmetry-related peptides perpendicular to the helical axis. The two chains were fit individually, as their relative orientations were rotated compared to the published model (teal). i, Fit of the published atomic model of Aβ42 type II filaments (PDB-ID: 7Q4M) into the reconstruction (grey mesh), shown for two C2 symmetry-related peptides perpendicular to the helical axis. The overall structure remains similar, with only subtle shifts in the backbone towards the N-termini and His13 side chain flips (cyan arrows) observed in our reconstruction.