ArticleProceedings of the National Academy of Sciences of the United States of America2020
Exploring the interplay between fibrillization and amorphous aggregation channels on the energy landscapes of tau repeat isoforms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Aqueous extractable nonfibrillar and sarkosyl extractable fibrillar Alzheimer's disease tau seeds have distinct properties.Acta neuropathologica communications · 2024Article
- Single-Molecule Characterization and Super-Resolution Imaging of Alzheimer's Disease-Relevant Tau Aggregates in Human Samples.Angewandte Chemie (International ed. in English) · 2024Article
- Structures of AT8 and PHF1 phosphomimetic tau: Insights into the posttranslational modification code of tau aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Biochemical approaches to assess the impact of post-translational modifications on pathogenic tau conformations using recombinant protein.Biochemical Society transactions · 2024Review
- OpenABC enables flexible, simplified, and efficient GPU accelerated simulations of biomolecular condensates.PLoS computational biology · 2023Article
- Neural potentials of proteins extrapolate beyond training data.The Journal of chemical physics · 2023Article
- OpenABC Enables Flexible, Simplified, and Efficient GPU Accelerated Simulations of Biomolecular Condensates.bioRxiv : the preprint server for biology · 2023Article
- Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia.International journal of molecular sciences · 2023Review
- Protein interactions: anything new?Essays in biochemistry · 2022Article
- Simulations of cross-amyloid aggregation of amyloid-β and islet amyloid polypeptide fragments.Biophysical journal · 2022Article
- Hyperphosphorylated tau self-assembles into amorphous aggregates eliciting TLR4-dependent responses.Nature communications · 2022Article
- Exploring the folding energy landscapes of heme proteins using a hybrid AWSEM-heme model.Journal of biological physics · 2022Article
- Computational Models for the Study of Protein Aggregation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders.Antioxidants (Basel, Switzerland) · 2021Review
- Theory and Practice of Coarse-Grained Molecular Dynamics of Biologically Important Systems.Biomolecules · 2021Article
- CHIP-mediated hyperubiquitylation of tau promotes its self-assembly into the insoluble tau filaments.Chemical science · 2021Article
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
- From System Modeling to System Analysis: The Impact of Resolution Level and Resolution Distribution in the Computer-Aided Investigation of Biomolecules.Frontiers in molecular biosciences · 2021Review
- The role of wild-type tau in Alzheimer's disease and related tauopathies.Journal of life sciences (Westlake Village, Calif.) · 2020Article
- Exploring the F-actin/CPEB3 interaction and its possible role in the molecular mechanism of long-term memory.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
4 authors.
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Abstract
Filaments made up of different isoforms of tau protein are associated with a variety of neurodegenerative diseases. Filaments made up of the 4R-tau isoform, which has four repeat regions (R1 to R4), are found in patients suffering from Alzheimer's disease, while filaments made of the 3R-tau isoform, which contains only three repeat units (R1, R3, and R4), are found in patients with Pick's disease (frontotemporal dementia). In this work, a predictive coarse-grained protein force field, the associative memory water-mediated structure and energy model (AWSEM), is used to study the energy landscapes of nucleation of the two different fibrils derived from patients with Pick's and Alzheimer's diseases. The landscapes for nucleating both fibril types contain amorphous oligomers leading to branched structures as well as prefibrillar oligomers. These two classes of oligomers differ in their structural details: The prefibrillar oligomers have more parallel in-register β-strands, which ultimately lead to amyloid fibrils, while the amorphous oligomers are characterized by a near random β-strand stacking, leading to a distinct amorphous phase. The landscape topography suggests that there must be significant structural reordering, or "backtracking," to transit from the amorphous aggregation channel to the fibrillization channel. Statistical mechanical perturbation theory allows us to evaluate the effects of changing concentration on the aggregation free-energy landscapes and to predict the effects of phosphorylation, which is known to facilitate the aggregation of tau repeats.
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