ArticleCommunications biology2021
Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates.
Article in Communications biology, 2021. 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, 45 citations in OpenAlex.
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- 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
- Kinetic Mechanism of Substoichiometric Inhibition of Huntingtin Exon-1 Protein Aggregation by Selenium Nanoparticles.Small science · 2025Article
- Protofibril Binding Peptides Recognize and Inhibit Huntingtin Amyloid FormationbioRxiv : the preprint server for biology · 2025Article
- Probing How Anti-huntingtin Antibodies Bind the Fibrillar Fuzzy Coat Using Solid-State NMR.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Direct Observation of Secondary Nucleation in Huntingtin Amyloid Formation by High-Speed Atomic Force Microscopy.Journal of the American Chemical Society · 2025Article
- Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease.Nature communications · 2024Article
- Integrative determination of the atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington's disease.bioRxiv : the preprint server for biology · 2024Article
- Structural Mapping of Protein Aggregates in Live Cells Modeling Huntington's Disease.Angewandte Chemie (International ed. in English) · 2024Article
- Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in-tissue multiscale 3D electron microscopy.Acta neuropathologica communications · 2024Article
- Nucleation of Huntingtin Aggregation Proceeds via Conformational Conversion of Pre-Formed, Sparsely-Populated Tetramers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Missing Wedge Completion via Unsupervised Learning with Coordinate Networks.International journal of molecular sciences · 2024Article
- Missing Wedge Completion via Unsupervised Learning with Coordinate Networks.bioRxiv : the preprint server for biology · 2024Article
- Solid-state nuclear magnetic resonance in the structural study of polyglutamine aggregation.Biochemical Society transactions · 2024Review
- The advent of preventive high-resolution structural histopathology by artificial-intelligence-powered cryogenic electron tomography.Frontiers in molecular biosciences · 2024Review
- Article
- The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity.Nature structural & molecular biology · 2023Article
- Quantitative NMR analysis of the kinetics of prenucleation oligomerization and aggregation of pathogenic huntingtin exon-1 protein.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Selective observation of semi-rigid non-core residues in dynamically complex mutant huntingtin protein fibrils.Journal of structural biology: X · 2022Article
- Insights into neurodegeneration from electron microscopy studies.Biochemical Society transactions · 2021Article
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 2 countries.
Funding
Abstract
Huntington disease (HD) is a neurodegenerative trinucleotide repeat disorder caused by an expanded poly-glutamine (polyQ) tract in the mutant huntingtin (mHTT) protein. The formation and topology of filamentous mHTT inclusions in the brain (hallmarks of HD implicated in neurotoxicity) remain elusive. Using cryo-electron tomography and subtomogram averaging, here we show that mHTT exon 1 and polyQ-only aggregates in vitro are structurally heterogenous and filamentous, similar to prior observations with other methods. Yet, we find filaments in both types of aggregates under ~2 nm in width, thinner than previously reported, and regions forming large sheets. In addition, our data show a prevalent subpopulation of filaments exhibiting a lumpy slab morphology in both aggregates, supportive of the polyQ core model. This provides a basis for future cryoET studies of various aggregated mHTT and polyQ constructs to improve their structure-based modeling as well as their identification in cells without fusion tags.
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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.