ArticleProceedings of the National Academy of Sciences of the United States of America2015
Conserved interdomain linker promotes phase separation of the multivalent adaptor protein Nck.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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101 citing papers in PubMed, 197 citations in OpenAlex.
- Multidomain Coupling Governs FoxP1 Assembly and Nuclear Compartmentalization.bioRxiv : the preprint server for biology · 2026Article
- The dynamic and heterogeneous composition of biomolecular condensates and its functional relevance.Nature reviews. Molecular cell biology · 2026Review
- Liquid-Liquid Phase Separation in Major Hallmarks of Cancer.Cell proliferation · 2026Review
- Molecular grammars of predicted intrinsically disordered regions that span the human proteome.Cell · 2026Article
- Biomolecular Condensates in and Around the ER-Golgi Interface.Sub-cellular biochemistry · 2026Review
- The regulatory principles, physiological functions, and phase transition of biomolecular condensates.Frontiers in cell and developmental biology · 2026Review
- Article
- Expanding the molecular grammar of polar residues and arginine in FUS phase separation.Nature chemical biology · 2025Article
- PSTP: accurate residue-level phase separation prediction using protein conformational and language model embeddings.Briefings in bioinformatics · 2025Article
- The Myotubularin Related Proteins and the Untapped Interaction Potential of Their Disordered C-Terminal Regions.Proteins · 2025Article
- Emergent microenvironments of nucleoli.Nucleus (Austin, Tex.) · 2024Review
- Structural Diversity and Distribution of Nuclear Matrix Constituent Protein Class Nuclear Lamina Proteins in Streptophytic Algae.Genome biology and evolution · 2024Article
- De novo designed YK peptides forming reversible amyloid for synthetic protein condensates in mammalian cells.Nature communications · 2024Article
- Liquid-liquid phase separation of microtubule-binding proteins in the regulation of spindle assembly.Cell proliferation · 2024Review
- Measurement of solubility product reveals the interplay of oligomerization and self-association for defining condensate formation.Molecular biology of the cell · 2024Article
- CytochromeiScience · 2024Article
- Interfacial exchange dynamics of biomolecular condensates are highly sensitive to client interactions.The Journal of chemical physics · 2024Article
- Precise prediction of phase-separation key residues by machine learning.Nature communications · 2024Article
- Expanding the molecular grammar of polar residues and arginine in FUS prion-like domain phase separation and aggregation.bioRxiv : the preprint server for biology · 2024Article
- Modulating Liquid-Liquid Phase Separation of Nck Adaptor Protein against EnteropathogenicACS central science · 2023Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The organization of membranes, the cytosol, and the nucleus of eukaryotic cells can be controlled through phase separation of lipids, proteins, and nucleic acids. Collective interactions of multivalent molecules mediated by modular binding domains can induce gelation and phase separation in several cytosolic and membrane-associated systems. The adaptor protein Nck has three SRC-homology 3 (SH3) domains that bind multiple proline-rich segments in the actin regulatory protein neuronal Wiskott-Aldrich syndrome protein (N-WASP) and an SH2 domain that binds to multiple phosphotyrosine sites in the adhesion protein nephrin, leading to phase separation. Here, we show that the 50-residue linker between the first two SH3 domains of Nck enhances phase separation of Nck/N-WASP/nephrin assemblies. Two linear motifs within this element, as well as its overall positively charged character, are important for this effect. The linker increases the driving force for self-assembly of Nck, likely through weak interactions with the second SH3 domain, and this effect appears to promote phase separation. The linker sequence is highly conserved, suggesting that the sequence determinants of the driving forces for phase separation may be generally important to Nck functions. Our studies demonstrate that linker regions between modular domains can contribute to the driving forces for self-assembly and phase separation of multivalent proteins.
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