ArticleNature structural & molecular biology2022
Identifying amyloid-related diseases by mapping mutations in low-complexity protein domains to pathologies.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Sex-stratified genome-wide meta-analysis identifies novel loci for cognitive decline in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Sequence-encoded conformational biases correlate with self-assembly modes of intrinsically disordered proteins.PNAS nexus · 2026Article
- Isoform-specific steric zippers drive aberrant assembly and mislocalization of shortened TDP-43.Science advances · 2026Article
- Structural basis for T-cell intracellular antigen-1 amyloid fibril formation revealed by cryo-electron microscopy.PNAS nexus · 2025Article
- Single-cell western blotting of cytoplasmic cytokeratin 8 proteoforms.The Analyst · 2025Article
- Single-cell western blotting of cytoplasmic cytokeratin 8 proteoforms.bioRxiv : the preprint server for biology · 2025Article
- Massive experimental quantification allows interpretable deep learning of protein aggregation.Science advances · 2025Article
- Deletions in Glial Fibrillary Acidic Protein Leading to Alterations in Intermediate Filament Assembly and Network Formation.International journal of molecular sciences · 2025Article
- Yeast Glucan Remodeling Protein Bgl2p: Amyloid Properties and the Mode of Attachment in Cell Wall.International journal of molecular sciences · 2024Article
- Article
- Sequence and structural determinants of RNAPII CTD phase-separation and phosphorylation by CDK7.Nature communications · 2024Article
- Massive experimental quantification of amyloid nucleation allows interpretable deep learning of protein aggregation.bioRxiv : the preprint server for biology · 2024Article
- Dan forms condensates in neuroblasts and regulates nuclear architecture and progenitor competence in vivo.Nature communications · 2024Article
- Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.Molecular neurodegeneration · 2024Article
- Review
- Neurofilaments as biomarkers in neurological disorders - towards clinical application.Nature reviews. Neurology · 2024Review
- How do disordered head domains assist in the assembly of intermediate filaments?Current opinion in cell biology · 2023Review
- Fibril structures of TFG protein mutants validate the identification of TFG as a disease-related amyloid protein by the IMPAcT method.PNAS nexus · 2023Article
- Cryo-EM structure of hnRNPDL-2 fibrils, a functional amyloid associated with limb-girdle muscular dystrophy D3.Nature communications · 2023Article
- The 2022 Lady Estelle Wolfson lectureship on neurofilaments.Journal of neurochemistry · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Proteins including FUS, hnRNPA2, and TDP-43 reversibly aggregate into amyloid-like fibrils through interactions of their low-complexity domains (LCDs). Mutations in LCDs can promote irreversible amyloid aggregation and disease. We introduce a computational approach to identify mutations in LCDs of disease-associated proteins predicted to increase propensity for amyloid aggregation. We identify several disease-related mutations in the intermediate filament protein keratin-8 (KRT8). Atomic structures of wild-type and mutant KRT8 segments confirm the transition to a pleated strand capable of amyloid formation. Biochemical analysis reveals KRT8 forms amyloid aggregates, and the identified mutations promote aggregation. Aggregated KRT8 is found in Mallory-Denk bodies, observed in hepatocytes of livers with alcoholic steatohepatitis (ASH). We demonstrate that ethanol promotes KRT8 aggregation, and KRT8 amyloids co-crystallize with alcohol. Lastly, KRT8 aggregation can be seeded by liver extract from people with ASH, consistent with the amyloid nature of KRT8 aggregates and the classification of ASH as an amyloid-related condition.
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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.