ArticleProceedings of the National Academy of Sciences of the United States of America2023
Polyubiquitin ligand-induced phase transitions are optimized by spacing between ubiquitin units.
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 17 papers.
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17 citing papers in PubMed, 19 citations in OpenAlex.
- Phosphorylation tunes strain-specific protein condensation during rotavirus replication organelle assembly.The EMBO journal · 2026Article
- Molecular architecture of meiotic pro-crossover factor HEI10 reveals coupling of higher-order assembly and ubiquitin chain formation.bioRxiv : the preprint server for biology · 2026Article
- STI1 domains coordinate partitioning of UBQLN2 into stress-induced condensates.bioRxiv : the preprint server for biology · 2026Article
- STI1 domain engages transient helices to mediate Dsk2 phase separation and proteasome condensation.The EMBO journal · 2026Article
- TBK1 Induces the Formation of Optineurin Filaments That Condensate with Polyubiquitin and LC3 for Cargo Sequestration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Biomolecular Phase Boundaries are Described by a Solubility Product That Accounts for Variable Stoichiometry and Soluble Oligomers.Journal of the American Chemical Society · 2025Article
- Biomolecular phase boundaries are described by a solubility product that accounts for variable stoichiometry and soluble oligomers.bioRxiv : the preprint server for biology · 2025Article
- Molecular basis of EWS interdomain self-association and its role in condensate formation.Protein science : a publication of the Protein Society · 2025Article
- Phosphorylation enables allosteric control of a viral condensate.bioRxiv : the preprint server for biology · 2025Article
- Protein quality control machinery: regulators of condensate architecture and functionality.Trends in biochemical sciences · 2025Review
- Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Dominance analysis to assess solute contributions to multicomponent phase equilibria.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate.bioRxiv : the preprint server for biology · 2024Article
- Insights into Molecular Diversity within the FUS/EWS/TAF15 Protein Family: Unraveling Phase Separation of the N-Terminal Low-Complexity Domain from RNA-Binding Protein EWS.Journal of the American Chemical Society · 2024Article
- Insights into Molecular Diversity within the FET Family: Unraveling Phase Separation of the N-Terminal Low Complexity Domain from RNA-Binding Protein EWS.bioRxiv : the preprint server for biology · 2023Article
- Polyubiquitin ligand-induced phase transitions are optimized by spacing between ubiquitin units.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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6 authors at 2 institutions in 1 country.
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Abstract
Biomolecular condensates form via multivalent interactions among key macromolecules and are regulated through ligand binding and/or posttranslational modifications. One such modification is ubiquitination, the covalent addition of ubiquitin (Ub) or polyubiquitin chains to target macromolecules. Specific interactions between polyubiquitin chains and partner proteins, including hHR23B, NEMO, and UBQLN2, regulate condensate assembly or disassembly. Here, we used a library of designed polyubiquitin hubs and UBQLN2 as model systems for determining the driving forces of ligand-mediated phase transitions. Perturbations to either the UBQLN2-binding surface of Ub or the spacing between Ub units reduce the ability of hubs to modulate UBQLN2 phase behavior. By developing an analytical model based on polyphasic linkage principles that accurately described the effects of different hubs on UBQLN2 phase separation, we determined that introduction of Ub to UBQLN2 condensates incurs a significant inclusion energetic penalty. This penalty antagonizes the ability of polyUb hubs to scaffold multiple UBQLN2 molecules and cooperatively amplify phase separation. The extent to which polyubiquitin hubs promote UBQLN2 phase separation is encoded in the spacings between Ub units. This spacing is modulated by chains of different linkages and designed chains of different architectures, thus illustrating how the ubiquitin code regulates functionality via the emergent properties of the condensate. The spacing in naturally occurring linear polyubiquitin chains is already optimized to promote phase separation with UBQLN2. We expect our findings to extend to other condensates, emphasizing the importance of ligand properties, including concentration, valency, affinity, and spacing between binding sites in studies and designs of condensates.
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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.