ArticleJournal of chemical information and modeling2021
Misfolding and Self-Assembly Dynamics of Microtubule-Binding Repeats of the Alzheimer-Related Protein Tau.
Article in Journal of chemical information and modeling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 47 citations in OpenAlex.
- Aberrant S293 Phosphorylation Drives Oligomerization of Tau Repeat R2: Insights from Molecular Dynamics Simulations.ACS chemical neuroscience · 2025Article
- Disrupting Amyloid Filaments of Tau by Means of Electric Fields.The journal of physical chemistry. B · 2025Article
- Computational exploration of the self-aggregation mechanisms of phenol-soluble modulins β1 and β2 in Staphylococcus aureus biofilms.Colloids and surfaces. B, Biointerfaces · 2025Article
- Computational insights into the aggregation mechanism of human calcitonin.International journal of biological macromolecules · 2025Article
- Effects of All-Atom and Coarse-Grained Molecular Mechanics Force Fields on Amyloid Peptide Assembly: The Case of a Tau K18 Monomer.Journal of chemical information and modeling · 2024Article
- Molecular Mechanism of Tau Misfolding and Aggregation: Insights from Molecular Dynamics Simulation.Current medicinal chemistry · 2024Review
- Pathological Impact of Tau Proteolytical Process on Neuronal and Mitochondrial Function: a Crucial Role in Alzheimer's Disease.Molecular neurobiology · 2023Review
- Differential Binding and Conformational Dynamics of Tau Microtubule-Binding Repeats with a Preformed Amyloid-β Fibril Seed.ACS chemical neuroscience · 2023Article
- A new electrochemical method that mimics phosphorylation of the core tau peptide K18 enables kinetic and structural analysis of intermediates and assembly.The Journal of biological chemistry · 2023Article
- Phosphorylation at Ser289 Enhances the Oligomerization of Tau Repeat R2.Journal of chemical information and modeling · 2023Article
- Review
- Phosphorylation of Tau R2 Repeat Destabilizes Its Binding to Microtubules: A Molecular Dynamics Simulation Study.ACS chemical neuroscience · 2023Article
- Investigation of the Structure of Full-Length Tau Proteins with Coarse-Grained and All-Atom Molecular Dynamics Simulations.ACS chemical neuroscience · 2023Article
- Molecular Insights into the Self-Assembly of Block Copolymer Suckerin Polypeptides into Nanoconfined β-Sheets.Small (Weinheim an der Bergstrasse, Germany) · 2022Article
- Exploring the misfolding and self-assembly mechanism of TTR (105-115) peptides by all-atom molecular dynamics simulation.Frontiers in molecular biosciences · 2022Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Pathological aggregation of intrinsically disordered tau protein, driven by the interactions between microtubule-binding (MTB) domains, is associated with Alzheimer's disease. The MTB domain contains either three or four repeats with sequence similarities. Compared to amyloid β, many aspects of the misfolding and aggregation mechanisms of tau are largely unknown. In this study, we systematically investigated the dynamics of monomer misfolding and dimerization of each MTB repeat using atomistic discrete molecular dynamic simulations. Our results revealed that all the four repeat monomers (R1-R4) were very dynamic, featuring frequent conformational conversion and lacking stable conformations. While R1, R2, and R4 monomers occasionally adopted partially helical conformations, R3 monomers frequently formed β-sheets. In dimerization simulations, R3 displayed the strongest aggregation propensity with high β-sheet contents, while R1 was the least prone to aggregation. The R2 and R4 dimers contained both helix and β-sheet structures. The β-sheets in R4 assemblies were dominant with β-hairpin conformation. In R2 and R3 dimers, intermolecular β-sheets were mainly driven by residues around the paired helical filament (PHF) regions. Residues around the PHF6* in R2 and PHF6 in R3 had significantly higher intermolecular contacts than other regions, suggesting that these residues play a key role in the amyloid aggregation of tau. Our results on the structural ensembles and early aggregation dynamics of each tau MTB repeat will help understand the nucleation and fibrillization of tau.
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