Fig. 1: Cryo-EM structure of rTg4510 Tau fibril.

a The workflow of the brain-derived rTg4510 Tau fibril purification and characterization. Immunohistochemistry staining of p-Tau (AT8) in the hippocampus of rTg4510 is shown on the left. Scale bar, 50 μm. The ex vivo Tau fibril was confirmed by immunogold negative-staining electron microscopy as shown on the right. Scale bar, 100 nm. b 2D class averages of rTg4510 Tau fibril (left) and minority untwist fibril (right). The percentages of the two types of ex vivo fibrils in the dataset and the half pitch of the rTg4510 Tau fibril are shown at the bottom. Scale bar, 5 nm. c 3D classification of the rTg4510 Tau fibril. Resolution of 3D reconstruction is indicated. Scale bar, 2 nm. d Top, diagram of human 0N4R Tau primary amino acid sequence. Residue 44 is followed by residue 103. All residues are numbered based on human 2N4R Tau isoform. N-terminal region, R4 region, R’ region, and C-terminal region are shown in black, with R1 region in orange, R2 region in blue and R3 in green. Middle, primary amino acid sequence of human 0N4R Tau with P301L mutation. Residues are colored as in top with P301L mutation indicated in purple. Thick connecting lines with arrowheads indicate β-strands. Bottom, atomic model of the rTg4510 Tau fibril overlaid with cryo-EM density map. Residues are colored as in top with islands A and B indicated in gray. e Comparison of the rTg4510 Tau with GPT fold (PDB:7P6A). The part using for comparison (residues 297–311) is zoomed in on the right panel. Local RMSD is indicated. f Zoom-in view of the corresponding region of (d, bottom). Distances of interactions between residues that stabilize the turn are indicated.