ArticleJournal of molecular biology2018
Tadpole-like Conformations of Huntingtin Exon 1 Are Characterized by Conformational Heterogeneity that Persists regardless of Polyglutamine Length.
Article in Journal of molecular biology, 2018. 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.
- Lipid composition controls the huntingtin exon 1 membrane-association and differentially modulates its flanking regions' dynamics.Protein science : a publication of the Protein Society · 2026Article
- Zika virus impairs non-homologous end joining and exacerbates DNA damage in neural progenitors derived from Huntington's disease iPSCs via mutant huntingtin-elicited Ku70/Ku80 complex disruption.Stem cell research & therapy · 2025Article
- TDP43 and huntingtin Exon-1 undergo a conformationally specific interaction that strongly alters the fibril formation of both proteins.The Journal of biological chemistry · 2024Article
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- Polyglutamine-mediated ribotoxicity disrupts proteostasis and stress responses in Huntington's disease.Nature cell biology · 2024Article
- The molecular basis for cellular function of intrinsically disordered protein regions.Nature reviews. Molecular cell biology · 2024Review
- Single-molecule FRET unmasks structural subpopulations and crucial molecular events during FUS low-complexity domain phase separation.Nature communications · 2023Article
- Article
- The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity.Nature structural & molecular biology · 2023Article
- Comparative molecular dynamics simulations of pathogenic and non-pathogenic huntingtin protein monomers and dimers.Frontiers in molecular biosciences · 2023Article
- Flexible Target Recognition of the Intrinsically Disordered DNA-Binding Domain of CytR Monitored by Single-Molecule Fluorescence Spectroscopy.The journal of physical chemistry. B · 2022Article
- Article
- Micellization: A new principle in the formation of biomolecular condensates.Frontiers in molecular biosciences · 2022Review
- Huntingtin and Its Partner Huntingtin-Associated Protein 40: Structural and Functional Considerations in Health and Disease.Journal of Huntington's disease · 2022Review
- Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1.Communications biology · 2021Article
- Adaptable P body physical states differentially regulate bicoid mRNA storage during early Drosophila development.Developmental cell · 2021Article
- Membrane Interactions Accelerate the Self-Aggregation of Huntingtin Exon 1 Fragments in a Polyglutamine Length-Dependent Manner.International journal of molecular sciences · 2021Article
- Site-Specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases.Chembiochem : a European journal of chemical biology · 2021Article
- Assessment of transferable forcefields for protein simulations attests improved description of disordered states and secondary structure propensities, and hints at multi-protein systems as the next challenge for optimization.Computational and structural biotechnology journal · 2021Article
- An Expanded Polyproline Domain Maintains Mutant Huntingtin SolubleFrontiers in molecular neuroscience · 2021Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Soluble huntingtin exon 1 (Httex1) with expanded polyglutamine (polyQ) engenders neurotoxicity in Huntington's disease. To uncover the physical basis of this toxicity, we performed structural studies of soluble Httex1 for wild-type and mutant polyQ lengths. Nuclear magnetic resonance experiments show evidence for conformational rigidity across the polyQ region. In contrast, hydrogen-deuterium exchange shows absence of backbone amide protection, suggesting negligible persistence of hydrogen bonds. The seemingly conflicting results are explained by all-atom simulations, which show that Httex1 adopts tadpole-like structures with a globular head encompassing the N-terminal amphipathic and polyQ regions and the tail encompassing the C-terminal proline-rich region. The surface area of the globular domain increases monotonically with polyQ length. This stimulates sharp increases in gain-of-function interactions in cells for expanded polyQ, and one of these interactions is with the stress-granule protein Fus. Our results highlight plausible connections between Httex1 structure and routes to neurotoxicity.
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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.