ArticleBiophysical journal2009
Mechanism of cis-inhibition of polyQ fibrillation by polyP: PPII oligomers and the hydrophobic effect.
Article in Biophysical journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 60 citations in OpenAlex.
- Chaperone-mediated remodelling of mutant huntingtin.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Comparative molecular dynamics simulations of pathogenic and non-pathogenic huntingtin protein monomers and dimers.Frontiers in molecular biosciences · 2023Article
- The evolution and polymorphism of mono-amino acid repeats in androgen receptor and their regulatory role in health and disease.Frontiers in medicine · 2022Review
- Threshold concentration and random collision determine the growth of the huntingtin inclusion from a stable core.Communications biology · 2021Article
- An Expanded Polyproline Domain Maintains Mutant Huntingtin SolubleFrontiers in molecular neuroscience · 2021Article
- Structural Model of the Proline-Rich Domain of Huntingtin Exon-1 Fibrils.Biophysical journal · 2020Article
- Article
- Nucleation Inhibition of Huntingtin Protein (htt) by Polyproline PPII Helices: A Potential Interaction with the N-Terminal α-Helical Region of Htt.Biochemistry · 2020Article
- 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
- Identification of a novel site of interaction between ataxin-3 and the amyloid aggregation inhibitor polyglutamine binding peptide 1.European journal of mass spectrometry (Chichester, England) · 2018Article
- Emerging β-Sheet Rich Conformations in Supercompact Huntingtin Exon-1 Mutant Structures.Journal of the American Chemical Society · 2017Article
- Review
- Article
- Nanoscale studies link amyloid maturity with polyglutamine diseases onset.Scientific reports · 2016Article
- Investigating Mutations to Reduce Huntingtin Aggregation by Increasing Htt-N-Terminal Stability and Weakening Interactions with PolyQ Domain.Computational and mathematical methods in medicine · 2016Article
- Polyglutamine Aggregation in Huntington Disease: Does Structure Determine Toxicity?Molecular neurobiology · 2015Review
- Solid-State Nuclear Magnetic Resonance on the Static and Dynamic Domains of Huntingtin Exon-1 Fibrils.Biochemistry · 2015Article
- Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state nuclear magnetic resonance.Biochemistry · 2014Article
- Monomeric, oligomeric and polymeric proteins in huntington disease and other diseases of polyglutamine expansion.Brain sciences · 2014Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
PolyQ peptides teeter between polyproline II (PPII) and beta-sheet conformations. In tandem polyQ-polyP peptides, the polyP segment tips the balance toward PPII, increasing the threshold number of Gln residues needed for fibrillation. To investigate the mechanism of cis-inhibition by flanking polyP segments on polyQ fibrillation, we examined short polyQ, polyP, and tandem polyQ-polyP peptides. These polyQ peptides have only three glutamines and cannot form beta-sheet fibrils. We demonstrate that polyQ-polyP peptides form small, soluble oligomers at high concentrations (as shown by size exclusion chromatography and diffusion coefficient measurements) with PPII structure (as shown by circular dichroism spectroscopy and (3)J(HN-C alpha) constants of Gln residues from constant time correlation spectroscopy NMR). Nuclear Overhauser effect spectroscopy and molecular modeling suggest that self-association of these peptides occurs as a result of both hydrophobic and steric effects. Pro side chains present three methylenes to solvent, favoring self-association of polyP through the hydrophobic effect. Gln side chains, with two methylene groups, can adopt a conformation similar to that of Pro side chains, also permitting self-association through the hydrophobic effect. Furthermore, steric clashes between Gln and Pro side chains to the C-terminal side of the polyQ segment favor adoption of the PPII-like structure in the polyQ segment. The conformational adaptability of the polyQ segment permits the cis-inhibitory effect of polyP segments on fibrillation by the polyQ segments in proteins such as huntingtin.
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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.