ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Functional interactions as a survival strategy against abnormal aggregation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed.
- Allosteric Modulation of Pathological Ataxin-3 Aggregation: A Path to Spinocerebellar Ataxia Type-3 Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synchronized motion of interface residues for evaluating protein-RNA complex binding affinity: Application to aptamer-mediated inhibition of TDP-43 aggregates.Protein science : a publication of the Protein Society · 2024Article
- Molecular Crowding: The History and Development of a Scientific Paradigm.Chemical reviews · 2024Review
- RNA-dependent proteome solubility maintenance inRNA biology · 2024Article
- Article
- Mutant Ataxin-3-Containing Aggregates (MATAGGs) in Spinocerebellar Ataxia Type 3: Dynamics of the Disorder.Molecular neurobiology · 2021Review
- Computational optimization of angiotensin-converting enzyme 2 for SARS-CoV-2 Spike molecular recognition.Computational and structural biotechnology journal · 2021Article
- Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association.Computational and structural biotechnology journal · 2021Article
- Aggregation is a Context-Dependent Constraint on Protein Evolution.Frontiers in molecular biosciences · 2021Article
- RNA as the stone guest of protein aggregation.Nucleic acids research · 2020Review
- Native aggregation is a common feature among triosephosphate isomerases of different species.Scientific reports · 2020Article
- Computational prediction of protein aggregation: Advances in proteomics, conformation-specific algorithms and biotechnological applications.Computational and structural biotechnology journal · 2020Review
- RNA as a key factor in driving or preventing self-assembly of the TAR DNA-binding protein 43.Journal of molecular biology · 2019Article
- Atomic force microscopy for single molecule characterisation of protein aggregation.Archives of biochemistry and biophysics · 2019Review
- Targeting Amyloid Aggregation: An Overview of Strategies and Mechanisms.International journal of molecular sciences · 2018Review
- Destabilizing the AXH Tetramer by Mutations: Mechanisms and Potential Antiaggregation Strategies.Biophysical journal · 2018Article
- Direct Conversion of an Enzyme from Native-like to Amyloid-like Aggregates within Inclusion Bodies.Biophysical journal · 2017Article
- Thermodynamic and kinetic stability of the Josephin Domain closed arrangement: evidences from replica exchange molecular dynamics.Biology direct · 2017Article
- Chaperones in Polyglutamine Aggregation: Beyond the Q-Stretch.Frontiers in neuroscience · 2017Review
- Ataxin-3 phosphorylation decreases neuronal defects in spinocerebellar ataxia type 3 models.The Journal of cell biology · 2016Article
Corrections and comments
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5 authors.
Funding
Abstract
Protein aggregation is under intense scrutiny because of its role in human disease. Although increasing evidence indicates that protein native states are highly protected against aggregation, the specific protection mechanisms are poorly understood. Insight into such mechanisms can be gained through study of the relatively few proteins that aggregate under native conditions. Ataxin-3, the protein responsible for Spinocerebellar ataxia type 3, a polyglutamine expansion disease, represents one of such examples. Polyglutamine expansion is central for determining solubility and aggregation rates of ataxin-3, but these properties are profoundly modulated by its N-terminal Josephin domain. This work aims at identifying the regions that promote Josephin fibrillogenesis and rationalizing the mechanisms that protect Josephin and nonexpanded ataxin-3 from aberrant aggregation. Using different biophysical techniques, aggregation propensity predictions and rational design of amino acid substitutions, we show that Josephin has an intrinsic tendency to fibrillize under native conditions and that fibrillization is promoted by two solvent-exposed patches, which are also involved in recognition of natural substrates, such as ubiquitin. Indeed, designed mutations at these patches or substrate binding significantly reduce Josephin aggregation kinetics. Our results provide evidence that protein nonpathologic function can play an active role in preventing aberrant fibrillization and suggest the molecular mechanism whereby this occurs in ataxin-3.
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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.