ArticleBiochemistry2022
Sequence-based Prediction of the Cellular Toxicity Associated with Amyloid Aggregation within Protein Condensates.
Article in Biochemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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
7 citing papers in PubMed, 14 citations in OpenAlex.
- FuzDrop: sequence-based prediction of the propensity of proteins for liquid-liquid phase separation and aggregation.Nature protocols · 2026Review
- Intrinsic disorder in CYP1B1 and its implications in primary congenital glaucoma pathogenesis.Journal of proteins and proteomics · 2025Article
- Unraveling the hydration dynamics of ACCBiophysical journal · 2024Article
- Amyloid Aggregation and Liquid-Liquid Phase Separation from the Perspective of Phase Transitions.The journal of physical chemistry. B · 2023Review
- FuzPred: a web server for the sequence-based prediction of the context-dependent binding modes of proteins.Nucleic acids research · 2023Article
- Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis.Nature communications · 2023Article
- Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Various neurological dysfunctions are associated with cytotoxic amyloid-containing aggregates formed through the irreversible maturation of protein condensates generated by phase separation. Here, we investigate the amino acid code for this cytotoxicity using TDP-43 deep-sequencing data. Within the droplet landscape framework, we analyze the impact of mutations in the amyloid core, aggregation hot-spot, and droplet-promoting residues on TDP-43 cytotoxicity. Our analysis suggests that TDP-43 mutations associated with low cytotoxicity moderately decrease the probability of droplet formation while increasing the probability of multimodal binding. These mutations promote both ordered and disordered binding modes, thus facilitating the conversion between the droplet and amyloid states. Based on this understanding, we develop an extension of the FuzDrop method for the sequence-based prediction of the cytotoxicity of aging condensates and test it over 20,000 TDP-43 variants. Our analysis provides insight into the amino acid code that regulates the cytotoxicity associated with the maturation of liquid-like condensates into amyloid-containing aggregates, suggesting that, at least in the case of TDP-43, mutations that promote aggregation tend to decrease cytotoxicity, while those that promote droplet formation tend to increase cytotoxicity.
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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.