ArticleProceedings of the National Academy of Sciences of the United States of America2024
Structures of AT8 and PHF1 phosphomimetic tau: Insights into the posttranslational modification code of tau aggregation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 33 citations in OpenAlex.
- Structural Hierarchy and Maturation of Amyloid Fibrils Revealed by Interface Descriptor Analysis.Journal of chemical information and modeling · 2026Article
- TogoPhosTAC as a delivery-ready platform for targeted protein dephosphorylation.Nature communications · 2026Article
- Water-Mediated Phosphoryl Wires Stabilize Pathological Tau Fibrils.Angewandte Chemie (International ed. in English) · 2026Article
- Structures and Dynamics of Tau Assemblies from Solid-State NMR.Accounts of chemical research · 2026Article
- The amyloid packing difference: A pairwise comparison metric for amyloid structures.Structure (London, England : 1993) · 2026Article
- Microglial mitochondria transfer to astrocytes via GPNMB-enriched extracellular vesicles alleviates cognitive deficits in tauopathy mice.Nature neuroscience · 2026Article
- Biophysical assessment of the molecular mechanisms of Tau aggregation and its role in Alzheimer's disease.Protein science : a publication of the Protein Society · 2026Review
- Article
- Phosphorylation Mimicking Mutations Cause TDP-43 to Adopt Different Fibril Conformations.bioRxiv : the preprint server for biology · 2026Article
- Full-length tau seeded by C-shaped tau fibrils is conformationally variable.The Journal of biological chemistry · 2026Article
- Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan.Acta neuropathologica · 2026Article
- Neuroprotective Mechanisms of Ficus deltoidea in an Alzheimer's Disease-Like Rat Model: Targeting Tau Hyperphosphorylation Through Glycogen Synthase Kinase-3 Beta and Protein Phosphatase 2A Regulation.Neurochemical research · 2026Article
- Big Tau: Structure, Evolutionary Divergence, and Emerging Roles in Cytoskeletal Dynamics and Tauopathies.Cells · 2026Review
- Heterogeneous Dynamics of the Fuzzy Coat of Full-Length Phospho-Mimetic Tau Fibrils.Journal of the American Chemical Society · 2026Article
- The Many Lives of a Single Sequence: Functional Plasticity Through Amyloid Polymorphism.Sub-cellular biochemistry · 2026Review
- Nucleolar aggregation of key neuropathological proteins in the postmortem neurodegenerative brain.Acta neuropathologica · 2025Article
- Systematic Review: Proteomics-Driven Multi-Omics Integration for Alzheimer's Disease Pathology and Precision Medicine.Neurology international · 2025Review
- Making tau amyloid models in vitro: a crucial and underestimated challenge.FEBS letters · 2025Review
- Circadian timing and entrainment properties of the SCN pacemaker in the PS19 mouse model of tau pathology.Experimental neurology · 2025Article
- Impact of Lysine Acetylation Mutations on the Structure of Full-Length Tau Fibrils.ACS chemical neuroscience · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The microtubule-associated protein tau aggregates into amyloid fibrils in Alzheimer's disease and other neurodegenerative diseases. In these tauopathies, tau is hyperphosphorylated, suggesting that this posttranslational modification (PTM) may induce tau aggregation. Tau is also phosphorylated in normal developing brains. To investigate how tau phosphorylation induces amyloid fibrils, here we report the atomic structures of two phosphomimetic full-length tau fibrils assembled without anionic cofactors. We mutated key Ser and Thr residues to Glu in two regions of the protein. One construct contains three Glu mutations at the epitope of the anti-phospho-tau antibody AT8 (AT8-3E tau), whereas the other construct contains four Glu mutations at the epitope of the antibody PHF1 (PHF1-4E tau). Solid-state NMR data show that both phosphomimetic tau mutants form homogeneous fibrils with a single set of chemical shifts. The AT8-3E tau rigid core extends from the R3 repeat to the C terminus, whereas the PHF1-4E tau rigid core spans R2, R3, and R4 repeats. Cryoelectron microscopy data show that AT8-3E tau forms a triangular multi-layered core, whereas PHF1-4E tau forms a triple-stranded core. Interestingly, a construct combining all seven Glu mutations exhibits the same conformation as PHF1-4E tau. Scalar-coupled NMR data additionally reveal the dynamics and shape of the fuzzy coat surrounding the rigid cores. These results demonstrate that specific PTMs induce structurally specific tau aggregates, and the phosphorylation code of tau contains redundancy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.