ArticleNature communications2024
Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- cGAS-STING pathway modulation: A new hope for neural regeneration.Neural regeneration research · 2026Article
- Pathogenic Proteins Through the Lens of NMR Spectroscopy: Structural and Functional Insights into Disease.Cell biochemistry and biophysics · 2025Review
- Post-Translational Modifications of Huntingtin: Mechanistic Insights and Therapeutic Opportunities in Huntington's Disease.International journal of molecular sciences · 2025Review
- FibrilPaint to determine the length of Tau amyloids in fluids.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Kinetic Mechanism of Substoichiometric Inhibition of Huntingtin Exon-1 Protein Aggregation by Selenium Nanoparticles.Small science · 2025Article
- Multiscale Simulations Elucidate the Mechanism of Polyglutamine Aggregation and the Role of Flanking Domains in Fibril Polymorphism.The journal of physical chemistry. B · 2025Article
- Pathological and Functional Brain Amyloids: A New Concept Explaining the Differences.International journal of molecular sciences · 2025Review
- A Coarse-Grained MD Model for Disorder-To-Order Transitions in PolyQ Aggregation.Journal of chemical theory and computation · 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
- Multiscale simulations elucidate the mechanism of polyglutamine aggregation and the role of flanking domains in fibril polymorphism.bioRxiv : the preprint server for biology · 2025Article
- Inhibitor-based modulation of huntingtin aggregation mechanisms mitigates fibril-induced cellular stress.Nature communications · 2025Article
- Role of Calmodulin in Neurodegeneration and Neuroprotection.Mini reviews in medicinal chemistry · 2025Review
- Integrative determination of atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington disease.Nature communications · 2024Article
- Solid-state nuclear magnetic resonance in the structural study of polyglutamine aggregation.Biochemical Society transactions · 2024Review
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8 authors.
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Abstract
Neurodegeneration in Huntington's disease (HD) is accompanied by the aggregation of fragments of the mutant huntingtin protein, a biomarker of disease progression. A particular pathogenic role has been attributed to the aggregation-prone huntingtin exon 1 (HTTex1), generated by aberrant splicing or proteolysis, and containing the expanded polyglutamine (polyQ) segment. Unlike amyloid fibrils from Parkinson's and Alzheimer's diseases, the atomic-level structure of HTTex1 fibrils has remained unknown, limiting diagnostic and treatment efforts. We present and analyze the structure of fibrils formed by polyQ peptides and polyQ-expanded HTTex1 in vitro. Atomic-resolution perspectives are enabled by an integrative analysis and unrestrained all-atom molecular dynamics (MD) simulations incorporating experimental data from electron microscopy (EM), solid-state NMR, and other techniques. Alongside the use of prior data, we report magic angle spinning NMR studies of glutamine residues of the polyQ fibril core and surface, distinguished via hydrogen-deuterium exchange (HDX). Our study provides a molecular understanding of the structure of the core as well as surface of aggregated HTTex1, including the fuzzy coat and polyQ-water interface. The obtained data are discussed in context of their implications for understanding the detection of such aggregates (diagnostics) as well as known biological properties of the fibrils.
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