ArticleNature structural & molecular biology2015
Polyalanine expansions drive a shift into α-helical clusters without amyloid-fibril formation.
Article in Nature structural & molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Tandem repeats in human brain evolution and disease susceptibility.Molecules and cells · 2026Review
- Cellular Functional Analyses ofHuman mutation · 2026Article
- Poly-alanine-tailing is a modifier of neurodegeneration caused by Listerin mutation.bioRxiv : the preprint server for biology · 2024Article
- Structural characterization of PHOX2B and its DNA interaction shed light on the molecular basis of the +7Ala variant pathogenicity in CCHS.Chemical science · 2024Article
- Therapeutic Effects of Plant Anthocyanin against Alzheimer's Disease and Modulate Gut Health, Short-Chain Fatty Acids.Nutrients · 2024Review
- Alternative low-populated conformations prompt phase transitions in polyalanine repeat expansions.Nature communications · 2024Article
- IFF: Identifying key residues in intrinsically disordered regions of proteins using machine learning.Protein science : a publication of the Protein Society · 2023Article
- The sequence context in poly-alanine regions: structure, function and conservation.Bioinformatics (Oxford, England) · 2022Article
- Conformational dynamics in the disordered region of human CPEB3 linked to memory consolidation.BMC biology · 2022Article
- Topological dynamics of an intrinsically disordered N-terminal domain of the human androgen receptor.Protein science : a publication of the Protein Society · 2022Article
- Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs.Communications biology · 2022Article
- Exogenous polyserine and polyleucine are toxic to recipient cells.Scientific reports · 2022Article
- Toxicity of internalized polyalanine to cells depends on aggregation.Scientific reports · 2021Article
- Amino acid homorepeats in proteins.Nature reviews. Chemistry · 2020Review
- Musashi-1: An Example of How Polyalanine Tracts Contribute to Self-Association in the Intrinsically Disordered Regions of RNA-Binding Proteins.International journal of molecular sciences · 2020Article
- A new mouse model of ARX dup24 recapitulates the patients' behavioral and fine motor alterations.Human molecular genetics · 2018Article
- Tandem repeats mediating genetic plasticity in health and disease.Nature reviews. Genetics · 2018Review
- TAR DNA-binding protein 43 (TDP-43) liquid-liquid phase separation is mediated by just a few aromatic residues.The Journal of biological chemistry · 2018Article
- A biosensor-based framework to measure latent proteostasis capacity.Nature communications · 2018Article
- Structure-based domain assignment in Leishmania infantum EndoG: characterization of a pH-dependent regulatory switch and a C-terminal extension that largely dictates DNA substrate preferences.Nucleic acids research · 2017Article
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12 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Polyglutamine (polyGln) expansions in nine human proteins result in neurological diseases and induce the proteins' tendency to form β-rich amyloid fibrils and intracellular deposits. Less well known are at least nine other human diseases caused by polyalanine (polyAla)-expansion mutations in different proteins. The mechanisms of how polyAla aggregates under physiological conditions remain unclear and controversial. We show here that aggregation of polyAla is mechanistically dissimilar to that of polyGln and hence does not exhibit amyloid kinetics. PolyAla assembled spontaneously into α-helical clusters with diverse oligomeric states. Such clustering was pervasive in cells irrespective of visible aggregate formation, and it disrupted the normal physiological oligomeric state of two human proteins natively containing polyAla: ARX and SOX3. This self-assembly pattern indicates that polyAla expansions chronically disrupt protein behavior by imposing a deranged oligomeric status.
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