ArticleJournal of molecular biology2015
Anti-PolyQ Antibodies Recognize a Short PolyQ Stretch in Both Normal and Mutant Huntingtin Exon 1.
Article in Journal of molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Huntingtin polyglutamine expansions misdirect axonal transport by perturbing motor and adaptor recruitment.iScience · 2026Article
- Transient Interdomain Interactions Modulate the Monomeric Structural Ensemble and Self-Assembly of Huntingtin Exon 1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification.Biomarker research · 2025Article
- The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity.Nature structural & molecular biology · 2023Article
- Salivary Huntingtin protein is uniquely associated with clinical features of Huntington's disease.Scientific reports · 2023Article
- Expression, Purification, Characterization and Cellular Uptake of MeCP2 Variants.The protein journal · 2022Article
- Huntingtin and Its Partner Huntingtin-Associated Protein 40: Structural and Functional Considerations in Health and Disease.Journal of Huntington's disease · 2022Review
- Characterization of Neuronal RNA Modifications during Non-associative Learning inACS central science · 2021Article
- Target-induced clustering activates Trim-Away of pathogens and proteins.Nature structural & molecular biology · 2021Article
- Mutant Huntingtin Is Cleared from the Brain via Active Mechanisms in Huntington Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Assessing average somatic CAG repeat instability at the protein level.Scientific reports · 2019Article
- The folding equilibrium of huntingtin exon 1 monomer depends on its polyglutamine tract.The Journal of biological chemistry · 2018Article
- Mutational analysis implicates the amyloid fibril as the toxic entity in Huntington's disease.Neurobiology of disease · 2018Article
- Identification of distinct conformations associated with monomers and fibril assemblies of mutant huntingtin.Human molecular genetics · 2018Article
- Tadpole-like Conformations of Huntingtin Exon 1 Are Characterized by Conformational Heterogeneity that Persists regardless of Polyglutamine Length.Journal of molecular biology · 2018Article
- A toxic mutant huntingtin species is resistant to selective autophagy.Nature chemical biology · 2017Article
- Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths.Journal of the American Chemical Society · 2017Article
- Polyglutamine expansion affects huntingtin conformation in multiple Huntington's disease models.Scientific reports · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Huntington's disease is caused by expansion of a polyglutamine (polyQ) repeat in the huntingtin protein. A structural basis for the apparent transition between normal and disease-causing expanded polyQ repeats of huntingtin is unknown. The "linear lattice" model proposed random-coil structures for both normal and expanded polyQ in the preaggregation state. Consistent with this model, the affinity and stoichiometry of the anti-polyQ antibody MW1 increased with the number of glutamines. An opposing "structural toxic threshold" model proposed a conformational change above the pathogenic polyQ threshold resulting in a specific toxic conformation for expanded polyQ. Support for this model was provided by the anti-polyQ antibody 3B5H10, which was reported to specifically recognize a distinct pathologic conformation of soluble expanded polyQ. To distinguish between these models, we directly compared binding of MW1 and 3B5H10 to normal and expanded polyQ repeats within huntingtin exon 1 fusion proteins. We found similar binding characteristics for both antibodies. First, both antibodies bound to normal, as well as expanded, polyQ in huntingtin exon 1 fusion proteins. Second, an expanded polyQ tract contained multiple epitopes for fragments antigen-binding (Fabs) of both antibodies, demonstrating that 3B5H10 does not recognize a single epitope specific to expanded polyQ. Finally, small-angle X-ray scattering and dynamic light scattering revealed similar binding modes for MW1 and 3B5H10 Fab-huntingtin exon 1 complexes. Together, these results support the linear lattice model for polyQ binding proteins, suggesting that the hypothesized pathologic conformation of soluble expanded polyQ is not a valid target for drug design.
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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.