ArticleeLife2026
Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments.
Article in eLife, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Cofactor-Free Tau Filaments Are Dynamic and Undergo Structural Evolution Driven by Thermodynamic Control.Journal of the American Chemical Society · 2026Article
- Rapid Fragment Screening byAngewandte Chemie (International ed. in English) · 2026Article
- The Pick fold in tau filaments from human MAPT mutants.Acta neuropathologica · 2026Article
- The amyloid packing difference: A pairwise comparison metric for amyloid structures.Structure (London, England : 1993) · 2026Article
- A metabolite extracted from Escherichia coli suppresses tau aggregation.The Biochemical journal · 2026Article
- Cysteines are critical determinants of spontaneous and seeded tau aggregation in cells.Research square · 2026Article
- Accessing intractable, phosphorylated intrinsically disordered proteins via a protease-cleavable inclusion body tag.Protein science : a publication of the Protein Society · 2026Article
- Tau catalyzes amyloid-β aggregation and toxicity in a polymorph-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Cysteines are critical determinants of spontaneous and seeded tau aggregation in cells.bioRxiv : the preprint server for biology · 2026Article
- Structural and mechanistic characterization of heparin interactions with tau fibrils.The Journal of biological chemistry · 2026Article
- Article
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
- Probing tau citrullination in Alzheimer's disease brains and mouse models of tauopathy.Acta neuropathologica · 2025Article
- To What Extent is Anfinsen's Thermodynamic Hypothesis Consistent With the Formation and Polymorphism of Amyloid Fibrils?Journal of molecular biology · 2025Review
- Seed structure and phosphorylation in the fuzzy coat impact tau seeding competency.Nature communications · 2025Article
- DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus.bioRxiv : the preprint server for biology · 2025Article
- Making tau amyloid models in vitro: a crucial and underestimated challenge.FEBS letters · 2025Review
- Serial amplification of tau filaments using Alzheimer's brain homogenates and C322A or C322S recombinant tau.FEBS letters · 2025Article
- Reversible tau hyperphosphorylation in hibernation: a blood biomarker and brain tissue study.Acta neuropathologica · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
The assembly of tau into amyloid filaments is associated with more than 20 neurodegenerative diseases, collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of brain-derived tau filaments revealed that specific structures define different diseases, triggering a quest for the development of experimental model systems that replicate the structures of disease. Here, we describe 12 phosphomimetic serine/threonine-to-aspartate mutations in tau, which we term PAD12, that collectively induce the in vitro assembly of full-length three-repeat tau into filaments with the same structure as paired helical filaments extracted from the brains of individuals with Alzheimer's disease. Solution-state nuclear magnetic resonance spectroscopy suggests that phosphomimetic mutations in the carboxy-terminal domain of tau may facilitate filament formation by disrupting an intramolecular interaction between two IVYK motifs. PAD12 tau can be used for both nucleation-dependent and multiple rounds of seeded assembly in vitro, as well as for the seeding of tau biosensor cells. PAD12 tau can be assembled into paired helical filaments under various shaking conditions, with the resulting filaments being stable for extended periods of time. They can be labelled with fluorophores and biotin. Tau filaments extracted from the brains of individuals with Alzheimer's disease have been known to be made of hyperphosphorylated and abnormally phosphorylated full-length tau, but it was not known if the presence of this post-translational modification is more than a mere correlation. Our findings suggest that hyperphosphorylation of tau may be sufficient for the formation of the Alzheimer tau fold. PAD12 tau will be a useful tool for the study of molecular mechanisms of neurodegeneration.
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