ArticleThe Journal of biological chemistry2016
An Intein-based Strategy for the Production of Tag-free Huntingtin Exon 1 Proteins Enables New Insights into the Polyglutamine Dependence of Httex1 Aggregation and Fibril Formation.
Article in The Journal of biological chemistry, 2016. 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, 48 citations in OpenAlex.
- 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
- The Effect of Protein Tagging on Aggregation and Phase Separation.Journal of cellular biochemistry · 2026Review
- Protofibril Binding Peptides Recognize and Inhibit Huntingtin Amyloid FormationbioRxiv : the preprint server for biology · 2025Article
- Direct Observation of Secondary Nucleation in Huntingtin Amyloid Formation by High-Speed Atomic Force Microscopy.Journal of the American Chemical Society · 2025Article
- Formation and persistence of polyglutamine aggregates in mistranslating cells.Nucleic acids research · 2021Article
- Nuclear and cytoplasmic huntingtin inclusions exhibit distinct biochemical composition, interactome and ultrastructural properties.Nature communications · 2021Article
- Pharmacological characterization of mutant huntingtin aggregate-directed PET imaging tracer candidates.Scientific reports · 2021Article
- Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates.Communications biology · 2021Article
- Correlative light and electron microscopy suggests that mutant huntingtin dysregulates the endolysosomal pathway in presymptomatic Huntington's disease.Acta neuropathologica communications · 2021Article
- Investigating Crosstalk Among PTMs Provides Novel Insight Into the Structural Basis Underlying the Differential Effects of Nt17 PTMs on Mutant Httex1 Aggregation.Frontiers in molecular biosciences · 2021Article
- An Expanded Polyproline Domain Maintains Mutant Huntingtin SolubleFrontiers in molecular neuroscience · 2021Article
- Effects of flanking sequences and cellular context on subcellular behavior and pathology of mutant HTT.Human molecular genetics · 2020Article
- Design and characterization of mutant and wildtype huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems.The Journal of biological chemistry · 2019Article
- N-terminal Huntingtin (Htt) phosphorylation is a molecular switch regulating Htt aggregation, helical conformation, internalization, and nuclear targeting.The Journal of biological chemistry · 2018Article
- Rapid and efficient production of cecropin A antibacterial peptide in Escherichia coli by fusion with a self-aggregating protein.BMC biotechnology · 2018Article
- Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy.Journal of visualized experiments : JoVE · 2018Article
- The 17-residue-long N terminus in huntingtin controls stepwise aggregation in solution and on membranes via different mechanisms.The Journal of biological chemistry · 2018Article
- Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths.Journal of the American Chemical Society · 2017Article
- Review
- Nanoscale studies link amyloid maturity with polyglutamine diseases onset.Scientific reports · 2016Article
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The first exon of the Huntingtin protein (Httex1) is one of the most actively studied Htt fragments because its overexpression in R6/2 transgenic mice has been shown to recapitulate several key features of Huntington disease. However, the majority of biophysical studies of Httex1 are based on assessing the structure and aggregation of fusion constructs where Httex1 is fused to large proteins, such as glutathione S-transferase, maltose-binding protein, or thioredoxin, or released in solution upon in situ cleavage of these proteins. Herein, we report an intein-based strategy that allows, for the first time, the rapid and efficient production of native tag-free Httex1 with polyQ repeats ranging from 7Q to 49Q. Aggregation studies on these proteins enabled us to identify interesting polyQ-length-dependent effects on Httex1 oligomer and fibril formation that were previously not observed using Httex1 fusion proteins or Httex1 proteins produced by in situ cleavage of fusion proteins. Our studies revealed the inability of Httex1-7Q/15Q to undergo amyloid fibril formation and an inverse correlation between fibril length and polyQ repeat length, suggesting possible polyQ length-dependent differences in the structural properties of the Httex1 aggregates. Altogether, our findings underscore the importance of working with tag-free Httex1 proteins and indicate that model systems based on non-native Httex1 sequences may not accurately reproduce the effect of polyQ repeat length and solution conditions on Httex1 aggregation kinetics and structural properties.
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