ArticlePLoS computational biology2005
Molecular origin of polyglutamine aggregation in neurodegenerative diseases.
Article in PLoS computational biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 108 citations in OpenAlex.
- GFP-free live neuron quantitative imaging reveals compartmentalization and growth dynamics of polyQ aggregates.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- DNA binding and mitotic phosphorylation protect polyglutamine proteins from assembly formation.Cell · 2025Article
- Hyperbaric Oxygen Therapy Attenuated the Motor Coordination and Cognitive Impairment of Polyglutamine Spinocerebellar Ataxia SCA17 Mice.Cerebellum (London, England) · 2024Article
- Big versus small: The impact of aggregate size in disease.Protein science : a publication of the Protein Society · 2023Review
- Protein Aggregation Inhibitors as Disease-Modifying Therapies for Polyglutamine Diseases.Frontiers in neuroscience · 2021Review
- "Trim"ming PolyQ proteins with engineered PML.Biotechnology and bioengineering · 2020Article
- Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE inhibition: a novel plausible route to anti-wrinkle activity of botox-like cosmetic active molecules.Molecular and cellular biochemistry · 2018Article
- Assembly of Huntingtin headpiece into α-helical bundles.Biointerphases · 2017Article
- Review
- An Exploration of the Universe of Polyglutamine Structures.PLoS computational biology · 2015Article
- Stable polyglutamine dimers can contain β-hairpins with interdigitated side chains-but not α-helices, β-nanotubes, β-pseudohelices, or steric zippers.Biophysical journal · 2014Article
- Computational approaches to understanding protein aggregation in neurodegeneration.Journal of molecular cell biology · 2014Review
- Coarse-grained simulations of the salt dependence of the radius of gyration of polyelectrolytes as models for biomolecules in aqueous solution.European biophysics journal : EBJ · 2013Article
- Microfluidic affinity and ChIP-seq analyses converge on a conserved FOXP2-binding motif in chimp and human, which enables the detection of evolutionarily novel targets.Nucleic acids research · 2013Article
- Physical chemistry of polyglutamine: intriguing tales of a monotonous sequence.Journal of molecular biology · 2012Review
- The interface of protein structure, protein biophysics, and molecular evolution.Protein science : a publication of the Protein Society · 2012Review
- Assessing the contribution of heterogeneous distributions of oligomers to aggregation mechanisms of polyglutamine peptides.Biophysical chemistry · 2011Article
- Critical nucleus size for disease-related polyglutamine aggregation is repeat-length dependent.Nature structural & molecular biology · 2011Article
- Stability tests on known and misfolded structures with discrete and all atom molecular dynamics simulations.Journal of molecular graphics & modelling · 2011Article
- Current understanding on the pathogenesis of polyglutamine diseases.Neuroscience bulletin · 2010Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expansion of polyglutamine (polyQ) tracts in proteins results in protein aggregation and is associated with cell death in at least nine neurodegenerative diseases. Disease age of onset is correlated with the polyQ insert length above a critical value of 35-40 glutamines. The aggregation kinetics of isolated polyQ peptides in vitro also shows a similar critical-length dependence. While recent experimental work has provided considerable insights into polyQ aggregation, the molecular mechanism of aggregation is not well understood. Here, using computer simulations of isolated polyQ peptides, we show that a mechanism of aggregation is the conformational transition in a single polyQ peptide chain from random coil to a parallel beta-helix. This transition occurs selectively in peptides longer than 37 glutamines. In the beta-helices observed in simulations, all residues adopt beta-strand backbone dihedral angles, and the polypeptide chain coils around a central helical axis with 18.5 +/- 2 residues per turn. We also find that mutant polyQ peptides with proline-glycine inserts show formation of antiparallel beta-hairpins in their ground state, in agreement with experiments. The lower stability of mutant beta-helices explains their lower aggregation rates compared to wild type. Our results provide a molecular mechanism for polyQ-mediated aggregation.
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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.