Extended Data Fig. 5: Cryo-EM structures of E46K α-syn fibrils and Tau fibrils in complex with heparin.
a, Top view and side views of the cryo-EM density map of the heparin-bound E46K α-syn fibrils. The additional densities for heparin are colored in red. b, Cross-section view of the structural model of heparin-bound E46K α-syn fibrils fitted in the density maps. The model is colored in grey. The density maps are restricted to areas within 2-Å radius of the E46K α-syn model, and combined with the heparin densities colored in red. The models and maps at heparin binding sites are zoomed-in. c, Top views and side views of the density maps of the heparin-bound Tau PHFs (Polymorph 1). d, Cross-section views of the structural models of heparin-bound Tau PHFs. e, Cross-section view of the structural model of Tau PHFs extracted from AD brains (PDB ID: 5O3L) fitted in the density map (EMDB ID: EMD-3741). The additional densities for heparin are colored in red. Other additional densities are colored in pink. f, Structural comparison of 1layer models of heparin bound (red) and EGCG bound (blue, PDB ID: 7UPG) Tau PHFs. The RMSD between two models are 1.296 Å over 150 C-α atoms. g, Density map of the heparin-bound Tau THFs (Polymorph 2). h, Density map of the heparin-bound Tau Polymorph 3. i, Model of Polymorph 3 fitted in the density map. The model is colored in grey. The density map is restricted to areas within 2-Å radius of the Tau models, and combined with the heparin densities colored in red. The model and additional densities at each heparin binding sites are zoomed-in. j, Top, density map of the heparin-bound Tau Polymorph 4 fibrils. The additional densities for heparin are colored in red. Bottom, model of Polymorph 4 fitted in the density map, shown as in panel i. k, Half pitch changes of α-syn (red) and Tau (blue) polymorphs. The 110 nm half pitch is indicated by grey dashed line.
