ArticleProceedings of the National Academy of Sciences of the United States of America2015
Regulation and aggregation of intrinsically disordered peptides.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 202 citations in OpenAlex.
- The microtubule nexus linking amyloid beta and tau: A simple and unifying theory for the underlying cause of Alzheimer's disease.PNAS nexus · 2026Article
- Sequence-Dependent Heterotypic Assemblies of Intrinsically Disordered Peptides.ChemistryEurope · 2026Article
- Electromagnetic Field Stimulation Effects on Intrinsically Disordered Proteins and Their Role in Aging and Neurodegeneration.Journal of biomedical science and engineering · 2025Article
- A comprehensive application of FiveFold for conformation ensemble-based protein structure prediction.Scientific reports · 2025Review
- Adsorption of Myelin Basic Protein on Model Myelin Membranes Reveals Weakening of van der Waals Interactions in a Lipid Ratio-Dependent Manner.Membranes · 2025Article
- The role of hydrophobic collapse in cytotoxic and functional amyloid oligomerization.Biophysical journal · 2025Article
- Analyses of exon 4a structure reveal unique properties of Big tau.bioRxiv : the preprint server for biology · 2025Article
- Tau Oligomers in Alzheimer's Disease: Modulation Effect of Osmolytes on Amplified Brain-Derived Tau Oligomers.ACS chemical neuroscience · 2025Article
- Ubiquitin-Proteasome System Dysregulation in Alzheimer's Disease Impacts Protein Abundance.bioRxiv : the preprint server for biology · 2025Article
- Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer's disease: a comprehensive review of the characteristics and therapeutic strategies.Translational neurodegeneration · 2025Review
- Chemical control of colloidal self-assembly driven by the electrosolvation force.Nature communications · 2025Article
- Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health.Metabolites · 2025Review
- The Role of Gut Microbiota-Derived Trimethylamine N-Oxide in the Pathogenesis and Treatment of Mild Cognitive Impairment.International journal of molecular sciences · 2025Review
- Intrinsic stiffness andPNAS nexus · 2025Article
- The role of trimethylamine N-oxide in disease pathogenesis and the therapeutic potential of traditional Chinese medicine.Frontiers in pharmacology · 2025Review
- Analyses of exon 4a structure reveal the properties of Big tau related to distribution, function and aggregation.Frontiers in molecular neuroscience · 2025Article
- Intrinsic Disorder and Other Malleable Arsenals of Evolved Protein Multifunctionality.Journal of molecular evolution · 2024Review
- In situ analysis of osmolyte mechanisms of proteome thermal stabilization.Nature chemical biology · 2024Article
- Review
- The Brain-Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review.Journal of clinical medicine · 2024Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Intrinsically disordered proteins (IDPs) are a unique class of proteins that have no stable native structure, a feature that allows them to adopt a wide variety of extended and compact conformations that facilitate a large number of vital physiological functions. One of the most well-known IDPs is the microtubule-associated tau protein, which regulates microtubule growth in the nervous system. However, dysfunctions in tau can lead to tau oligomerization, fibril formation, and neurodegenerative disease, including Alzheimer's disease. Using a combination of simulations and experiments, we explore the role of osmolytes in regulating the conformation and aggregation propensities of the R2/wt peptide, a fragment of tau containing the aggregating paired helical filament (PHF6*). We show that the osmolytes urea and trimethylamine N-oxide (TMAO) shift the population of IDP monomer structures, but that no new conformational ensembles emerge. Although urea halts aggregation, TMAO promotes the formation of compact oligomers (including helical oligomers) through a newly proposed mechanism of redistribution of water around the perimeter of the peptide. We put forth a "superposition of ensembles" hypothesis to rationalize the mechanism by which IDP structure and aggregation is regulated in the cell.
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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.