ArticleThe Journal of biological chemistry2014
Biophysical underpinnings of the repeat length dependence of polyglutamine amyloid formation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Targeting Protein Aggregates with Natural Products: An Optional Strategy for Neurodegenerative Diseases.International journal of molecular sciences · 2023Pooled it
- A tunable affinity fusion tag for protein self-assembly.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of Polyglutamine Misfolding with D-Enantiomeric Peptides Identified by Mirror Image Phage Display Selection.Biomolecules · 2022Article
- Huntingtin Polyglutamine Fragments Are a Substrate for Hsp104 in Saccharomyces cerevisiae.Molecular and cellular biology · 2021Article
- Protein assembly systems in natural and synthetic biology.BMC biology · 2020Review
- Nucleation Inhibition of Huntingtin Protein (htt) by Polyproline PPII Helices: A Potential Interaction with the N-Terminal α-Helical Region of Htt.Biochemistry · 2020Article
- Conformational studies of pathogenic expanded polyglutamine protein deposits from Huntington's disease.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Lipid Membranes Influence the Ability of Small Molecules To Inhibit Huntingtin Fibrillization.Biochemistry · 2019Article
- Mutational analysis implicates the amyloid fibril as the toxic entity in Huntington's disease.Neurobiology of disease · 2018Article
- Chromosomal instability causes sensitivity to protein folding stress and ATP depletion.Biology open · 2018Article
- Review
- Backbone Engineering within a Latent β-Hairpin Structure to Design Inhibitors of Polyglutamine Amyloid Formation.Journal of molecular biology · 2017Article
- The Aggregation Free Energy Landscapes of Polyglutamine Repeats.Journal of the American Chemical Society · 2016Article
- Rapid α-oligomer formation mediated by the Aβ C terminus initiates an amyloid assembly pathway.Nature communications · 2016Article
- 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.The Journal of biological chemistry · 2016Article
- Delayed emergence of subdiffraction-sized mutant huntingtin fibrils following inclusion body formation.Quarterly reviews of biophysics · 2016Article
- CAMELOT: A machine learning approach for coarse-grained simulations of aggregation of block-copolymeric protein sequences.The Journal of chemical physics · 2015Article
- Q&A: repeat-containing proteins.Nature structural & molecular biology · 2015Article
- Molecular interaction between the chaperone Hsc70 and the N-terminal flank of huntingtin exon 1 modulates aggregation.The Journal of biological chemistry · 2015Article
- Architecture of polyglutamine-containing fibrils from time-resolved fluorescence decay.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
There are now 10 expanded CAG repeat diseases in which both disease risk and age of onset are strongly dependent on the repeat length of the polyglutamine (polyQ) sequence in the disease protein. Large, polyQ-rich inclusions in patient brains and in cell and animal models are consistent with the involvement of polyQ aggregation in the disease mechanism. This possibility is reinforced by studies showing strong repeat length dependence to the aggregation process, qualitatively mirroring the repeat length dependence of disease risk. Our understanding of the underlying biophysical principles that mediate the repeat length dependence of aggregation, however, is far from complete. A previous study of simple polyQ peptides showed that N*, the size of the critical nucleus that controls onset of aggregation, decreases from unfavorable tetramer to favorable monomer over the range Q23 to Q26. These data, however, do not explain why, for all peptides exhibiting N* ∼ 1, spontaneous aggregation rates continue to increase with increasing repeat length. Here we describe a novel kinetics analyses that maps out the nonlinear dependence with repeat length of a nucleation efficiency term that is likely related to aspects of nucleus structure. This trend accounts for why nucleus size increases to tetrameric at repeat lengths of Q23 or below. Intriguingly, both aggregation and age of onset trend with repeat length in similar ways, exhibiting large changes per added Gln at low repeat lengths and small changes per added Gln at relatively long repeat lengths. Fibril stability also increases with repeat length in a nonlinear fashion.
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Registered trials
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