ArticleThe journal of physical chemistry. B2015
Tau assembly: the dominant role of PHF6 (VQIVYK) in microtubule binding region repeat R3.
Article in The journal of physical chemistry. B, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 183 citations in OpenAlex.
- The Enigma of Big Tau Exon 4a: Genomic Architecture, Biophysical Identity, and Unique Evolutionary Mechanisms.Biomolecules · 2026Review
- Targeted nanomedicine strategies for Alzheimer's disease therapy.Discover nano · 2026Review
- Disentangling Intrachain Folding from Interchain Assembly through Multidimensional Visualization.The journal of physical chemistry. B · 2026Article
- Tau profiling of brain extracellular vesicles reveals PHF6 peptide as core for pathological tau seeding in Alzheimer's disease.Journal of biomedical science · 2026Article
- amyloid-predict and LLPS-predict: Predicting phase separation propensities in the intrinsically disordered proteome.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Drosophila wing is a high-throughput and versatile screening tool for Tau-mediated disease mechanisms and drug discovery.Disease models & mechanisms · 2026Article
- Natural L-Hexapeptides with Therapeutic Potential for Alzheimer's Disease and Tauopathies.ACS omega · 2025Article
- Tau4RD fibril polymorphism is imprinted during early aggregation.bioRxiv : the preprint server for biology · 2025Article
- Tau-Targeted Therapeutic Strategies: Mechanistic Targets, Clinical Pipelines, and Analysis of Failures.Cells · 2025Review
- Disrupting Amyloid Filaments of Tau by Means of Electric Fields.The journal of physical chemistry. B · 2025Article
- Analyses of exon 4a structure reveal unique properties of Big tau.bioRxiv : the preprint server for biology · 2025Article
- Intrinsic aggregation and propagation of unmodified tau peptides: R2R3 as a minimal model system.Biophysical journal · 2025Article
- Hydrophobicity in Intrinsically Disordered Protein Force Fields: Implications for Conformational Ensembles and Protein-Protein Interactions.The journal of physical chemistry. B · 2025Article
- Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.Translational neurodegeneration · 2025Review
- Structure-specific Mini-Prion Model for Alzheimer's Disease Tau Fibrils.bioRxiv : the preprint server for biology · 2025Article
- Nanoplatforms Targeting Intrinsically Disordered Protein Aggregation for Translational Neuroscience Applications.Nanomaterials (Basel, Switzerland) · 2025Review
- Water-directed pinning is key to tau prion formation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inducers and modulators of protein aggregation in Alzheimer's disease - Critical tools for understanding the foundations of aggregate structures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Geometry based prediction of tau protein sites and motifs associated with misfolding and aggregation.Scientific reports · 2025Article
- Analyses of exon 4a structure reveal the properties of Big tau related to distribution, function and aggregation.Frontiers in molecular neuroscience · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Self-aggregation of the microtubule-binding protein Tau reduces its functionality and is tightly associated with Tau-related diseases, termed tauopathies. Tau aggregation is also strongly associated with two nucleating six-residue segments, namely PHF6 (VQIVYK) and PHF6* (VQIINK). In this paper, using experiments and computational modeling, we study the self-assembly of individual and binary mixtures of Tau fragments containing PHF6* (R2/wt; (273)GKVQIINKKLDL(284)) and PHF6 (R3/wt; (306)VQIVYKPVDLSK(317)) and a mutant R2/ΔK280 associated with a neurodegenerative tauopathy. The initial stage of aggregation is probed by ion-mobility mass spectrometry, the kinetics of aggregation monitored with Thioflavin T assays, and the morphology of aggregates visualized by transmission electron microscopy. Insights into the structure of early aggregates and the factors stabilizing the aggregates are obtained from replica exchange molecular dynamics simulations. Our data suggest that R3/wt has a much stronger aggregation propensity than either R2/wt or R2/ΔK280. Heterodimers containing R3/wt are less stable than R3/wt homodimers but much more stable than homodimers of R2/wt and R2/ΔK280, suggesting a possible role of PHF6*-PHF6 interactions in initiating the aggregation of full-length Tau. Lastly, R2/ΔK280 binds more strongly to R3/wt than R2/wt, suggesting a possible mechanism for a pathological loss of normal Tau function.
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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.