ArticleProceedings of the National Academy of Sciences of the United States of America2016
Protein structural and surface water rearrangement constitute major events in the earliest aggregation stages of tau.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed.
- Hydraulic Activation of the AsLOV2 Photoreceptor.bioRxiv : the preprint server for biology · 2025Article
- DEER of Singly Labelled Proteins to Evaluate Supramolecular Packing of Amyloid Fibrils.bioRxiv : the preprint server for biology · 2025Article
- Structure-specific Mini-Prion Model for Alzheimer's Disease Tau Fibrils.bioRxiv : the preprint server for biology · 2025Article
- Water-directed pinning is key to tau prion formation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Diverse influences on tau aggregation and implications for disease progression.Genes & development · 2025Review
- Ensemble structure of the N-terminal domain (1-267) of FUS in a biomolecular condensate.Biophysical journal · 2024Article
- Article
- Design of Soft Material Surfaces with Rationally Tuned Water Diffusivity.ACS central science · 2023Article
- Identifying Biological and Biophysical Features of Different Maturation States of α-Synuclein Amyloid Fibrils.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Pathway Dependence of the Formation and Development of Prefibrillar Aggregates in Insulin B Chain.Molecules (Basel, Switzerland) · 2022Article
- Multistep growth of amyloid intermediates and its inhibition toward exploring therapeutic way: A case study using insulin B chain and fibrinogen.Biophysics and physicobiology · 2022Article
- Structural Analysis and Conformational Dynamics of Short Helical Hyperphosphorylated Segments of Tau Protein (Sequence 254-290) in Alzheimer's Disease: A Molecular Dynamics Simulation Study.Frontiers in molecular biosciences · 2022Article
- Structural and mechanistic insights into amyloid-β and α-synuclein fibril formation and polyphenol inhibitor efficacy in phospholipid bilayers.The FEBS journal · 2022Article
- Liquid-Liquid Phase Separation of Tau Driven by Hydrophobic Interaction Facilitates Fibrillization of Tau.Journal of molecular biology · 2021Article
- Patterns of flea infestation in rodents and insectivores from intensified agro-ecosystems, Northwest Spain.Parasites & vectors · 2021Article
- Traumatic Brain Injury: Mechanisms of Glial Response.Frontiers in physiology · 2021Review
- Structures of Pathological and Functional Amyloids and Prions, a Solid-State NMR Perspective.Frontiers in molecular neuroscience · 2021Review
- Hydration and Dynamics of Full-Length Tau Amyloid Fibrils Investigated by Solid-State Nuclear Magnetic Resonance.Biochemistry · 2020Article
- Electrostatic Environment of Proteorhodopsin Affects the pKa of Its Buried Primary Proton Acceptor.Biophysical journal · 2020Article
- Structure and Aggregation Mechanisms in Amyloids.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein aggregation plays a critical role in the pathogenesis of neurodegenerative diseases, and the mechanism of its progression is poorly understood. Here, we examine the structural and dynamic characteristics of transiently evolving protein aggregates under ambient conditions by directly probing protein surface water diffusivity, local protein segment dynamics, and interprotein packing as a function of aggregation time, along the third repeat domain and C terminus of Δtau187 spanning residues 255-441 of the longest isoform of human tau. These measurements were achieved with a set of highly sensitive magnetic resonance tools that rely on site-specific electron spin labeling of Δtau187. Within minutes of initiated aggregation, the majority of Δtau187 that is initially homogeneously hydrated undergoes structural transformations to form partially structured aggregation intermediates. This is reflected in the dispersion of surface water dynamics that is distinct around the third repeat domain, found to be embedded in an intertau interface, from that of the solvent-exposed C terminus. Over the course of hours and in a rate-limiting process, a majority of these aggregation intermediates proceed to convert into stable β-sheet structured species and maintain their stacking order without exchanging their subunits. The population of β-sheet structured species is >5% within 5 min of aggregation and gradually grows to 50-70% within the early stages of fibril formation, while they mostly anneal block-wisely to form elongated fibrils. Our findings suggest that the formation of dynamic aggregation intermediates constitutes a major event occurring in the earliest stages of tau aggregation that precedes, and likely facilitates, fibril formation and growth.
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.