ArticleProceedings of the National Academy of Sciences of the United States of America2023
Phosphorylation sites are evolutionary checkpoints against liquid-solid transition in protein condensates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Molecular Origins of pH Gradients in Charge-Regulated Biomolecular Condensates.bioRxiv : the preprint server for biology · 2026Article
- Phosphorylation tunes strain-specific protein condensation during rotavirus replication organelle assembly.The EMBO journal · 2026Article
- Engineering Design of Artificial Phase-Separating Proteins.Biotechnology journal · 2026Review
- Origin of the ionic-strength dependent reentrant behavior in the liquid-liquid phase separation of uncharged intrinsically disordered proteins.Communications chemistry · 2026Article
- Droplet growth, Ostwald's rule, and emergence of order in Fused in Sarcoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- AMPK alters proteasome phosphorylation status and prevents persistent proteasome condensates.Genetics · 2025Article
- Evolution of a fuzzy ribonucleoprotein complex in viral assembly.bioRxiv : the preprint server for biology · 2025Article
- Elucidation of the Molecular Interaction Network Underlying Full-Length FUS Conformational Transitions and Its Phase Separation Using Atomistic Simulations.The journal of physical chemistry. B · 2025Article
- The Origin of the Ionic-strength Dependent Reentrant Behavior in Liquid-Liquid Phase Separation of Uncharged IDPs.bioRxiv : the preprint server for biology · 2025Article
- Expanding the molecular grammar of polar residues and arginine in FUS phase separation.Nature chemical biology · 2025Article
- Submolecular Resolution of β‑Sheet Plasticity: Decoding Mutations and PTMs in Protein Aggregation Disorders.ACS central science · 2025Article
- Phosphorylation enables allosteric control of a viral condensate.bioRxiv : the preprint server for biology · 2025Article
- Molecular simulations of enzymatic phosphorylation of disordered proteins and their condensates.Nature communications · 2025Article
- Semaphorin 6A phase separation sustains a histone lactylation-dependent lactate buildup in pathological angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Phase Separation Clustering of Poly Ubiquitin Cargos on Ternary Mixture Lipid Membranes by Synthetically Cross-Linked Ubiquitin Binder Peptides.Biochemistry · 2025Article
- Separation of sticker-spacer energetics governs the coalescence of metastable condensates.Biophysical journal · 2025Article
- Recent Progress in Modeling and Simulation of Biomolecular Crowding and Condensation Inside Cells.Journal of chemical information and modeling · 2024Review
- Sequence complexity and monomer rigidity control the morphologies and aging dynamics of protein aggregates.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- IGF2BP1 phosphorylation in the disordered linkers regulates ribonucleoprotein condensate formation and RNA metabolism.Nature communications · 2024Article
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
Assemblies of multivalent RNA-binding protein fused in sarcoma (FUS) can exist in the functional liquid-like state as well as less dynamic and potentially toxic amyloid- and hydrogel-like states. How could then cells form liquid-like condensates while avoiding their transformation to amyloids? Here, we show how posttranslational phosphorylation can provide a "handle" that prevents liquid-solid transition of intracellular condensates containing FUS. Using residue-specific coarse-grained simulations, for 85 different mammalian FUS sequences, we show how the number of phosphorylation sites and their spatial arrangement affect intracluster dynamics preventing conversion to amyloids. All atom simulations further confirm that phosphorylation can effectively reduce the β-sheet propensity in amyloid-prone fragments of FUS. A detailed evolutionary analysis shows that mammalian FUS PLDs are enriched in amyloid-prone stretches compared to control neutrally evolved sequences, suggesting that mammalian FUS proteins evolved to self-assemble. However, in stark contrast to proteins that do not phase-separate for their function, mammalian sequences have phosphosites in close proximity to these amyloid-prone regions. These results suggest that evolution uses amyloid-prone sequences in prion-like domains to enhance phase separation of condensate proteins while enriching phosphorylation sites in close proximity to safeguard against liquid-solid transitions.
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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.