ArticleNature structural & molecular biology2023
The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Mitochondrial DNA homeostasis: A novel therapeutic target for neurodegenerative diseases.Neural regeneration research · 2026Article
- From Food Additives to Neurodegeneration: The Emerging Role of Polyphosphates in Tauopathies.ACS chemical neuroscience · 2026Review
- Transient tertiary structure in intrinsically disordered proteins revealed by multithermal enhanced sampling.Nature communications · 2026Article
- Fast Ultra-SelectiveAngewandte Chemie (International ed. in English) · 2026Article
- 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
- Microglial immune memory in Parkinson's and Huntington's diseases: epigenetics, triggers, and therapies.Epigenomics · 2025Review
- Transient Interdomain Interactions Modulate the Monomeric Structural Ensemble and Self-Assembly of Huntingtin Exon 1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- AlphaFold prediction of structural ensembles of disordered proteins.Nature communications · 2025Article
- Site-Specific Incorporation of Fluorinated Prolines into Proteins and Their Impact on Neighbouring Residues.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin.Nature communications · 2025Article
- Weighted families of contact maps to characterize conformational ensembles of (highly-)flexible proteins.Bioinformatics (Oxford, England) · 2024Article
- Quantifying surface tension and viscosity in biomolecular condensates by FRAP-ID.Biophysical journal · 2024Article
- Endosome mediated nucleocytoplasmic trafficking and endomembrane allocation is crucial to polyglutamine toxicity.Cell biology and toxicology · 2024Article
- Alternative low-populated conformations prompt phase transitions in polyalanine repeat expansions.Nature communications · 2024Article
- The molecular basis for cellular function of intrinsically disordered protein regions.Nature reviews. Molecular cell biology · 2024Review
- Article
- The N17 domain of huntingtin as a multifaceted player in Huntington's disease.Frontiers in molecular biosciences · 2024Review
- Article
- Pathogen-specific structural features ofmBio · 2023Article
- Comparative molecular dynamics simulations of pathogenic and non-pathogenic huntingtin protein monomers and dimers.Frontiers in molecular biosciences · 2023Article
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21 authors.
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Abstract
Huntington's disease is a neurodegenerative disorder caused by a CAG expansion in the first exon of the HTT gene, resulting in an extended polyglutamine (poly-Q) tract in huntingtin (httex1). The structural changes occurring to the poly-Q when increasing its length remain poorly understood due to its intrinsic flexibility and the strong compositional bias. The systematic application of site-specific isotopic labeling has enabled residue-specific NMR investigations of the poly-Q tract of pathogenic httex1 variants with 46 and 66 consecutive glutamines. Integrative data analysis reveals that the poly-Q tract adopts long α-helical conformations propagated and stabilized by glutamine side chain to backbone hydrogen bonds. We show that α-helical stability is a stronger signature in defining aggregation kinetics and the structure of the resulting fibrils than the number of glutamines. Our observations provide a structural perspective of the pathogenicity of expanded httex1 and pave the way to a deeper understanding of poly-Q-related diseases.
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