ArticleNucleic acids research2021
Interplay of folded domains and the disordered low-complexity domain in mediating hnRNPA1 phase separation.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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94 citing papers in PubMed, 173 citations in OpenAlex.
- Liquid-Liquid Phase Separation-Enhanced Multienzyme Catalysis: Mechanisms and Applications.ChemSusChem · 2026Review
- Assessment of Aggregation- and Condensation-Prone Regions of Proteins Involved in Neurodegenerative, Neurological and Mental-State Diseases.Biomolecules · 2026Article
- The Effect of Protein Tagging on Aggregation and Phase Separation.Journal of cellular biochemistry · 2026Review
- In Search of Shape in the Unshaped: Constructing Ensembles of Intrinsically Disordered Proteins.Biophysics reviews · 2026Article
- Competition between protein-RNA clustering and phase separation drives re-entrant phase behavior of hnRNPA1.Nature communications · 2026Article
- [Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Folded domains impose structural heterogeneity and attenuated dynamics in biomolecular condensates.Nature communications · 2026Article
- Phosphotyrosine proteomics reveals novel Zap70 and Itk pathway targets downstream of TCR and CAR in Jurkat T cells.Scientific reports · 2026Article
- STI1 domain engages transient helices to mediate Dsk2 phase separation and proteasome condensation.The EMBO journal · 2026Article
- IDPForge: Deep Learning of Proteins with Global and Local Regions of Disorder.bioRxiv : the preprint server for biology · 2026Article
- Oligomerization of PER2 as a dynamic mode of regulation of the mammalian circadian clock.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- DNA binding and dimerization of the SOG1 NAC domain are functionally linked with its ability to undergo liquid-liquid phase separation.Nucleic acids research · 2026Article
- Acidosis promotes exon skipping through sequestering SR-rich splicing factors in nuclear speckles.Frontiers in molecular biosciences · 2026Article
- Fluorescent protein and peptide tags alter condensate formation and dynamics in vivo and in vitro.EMBO reports · 2026Article
- Biomolecular Condensates Can Induce Local Membrane Potentials.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Heterogeneous Folding Intermediates Govern the Conformational Pathway of the RNA Recognition Motif Domain of the Ewing Sarcoma Protein.Biomolecules · 2025Article
- Molecular insights on the mechanism of α1-antitrypsin condensate formation and maturation.PLoS computational biology · 2025Article
- How the Extent of Protein Folding and Oligomerization Modulate Condensate Formation and Properties.The journal of physical chemistry letters · 2025Article
- Molecular basis of EWS interdomain self-association and its role in condensate formation.Protein science : a publication of the Protein Society · 2025Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Liquid-liquid phase separation underlies the membrane-less compartmentalization of cells. Intrinsically disordered low-complexity domains (LCDs) often mediate phase separation, but how their phase behavior is modulated by folded domains is incompletely understood. Here, we interrogate the interplay between folded and disordered domains of the RNA-binding protein hnRNPA1. The LCD of hnRNPA1 is sufficient for mediating phase separation in vitro. However, we show that the folded RRM domains and a folded solubility-tag modify the phase behavior, even in the absence of RNA. Notably, the presence of the folded domains reverses the salt dependence of the driving force for phase separation relative to the LCD alone. Small-angle X-ray scattering experiments and coarse-grained MD simulations show that the LCD interacts transiently with the RRMs and/or the solubility-tag in a salt-sensitive manner, providing a mechanistic explanation for the observed salt-dependent phase separation. These data point to two effects from the folded domains: (i) electrostatically-mediated interactions that compact hnRNPA1 and contribute to phase separation and (ii) increased solubility at higher ionic strengths mediated by the folded domains. The interplay between disordered and folded domains can modify the dependence of phase behavior on solution conditions and can obscure signatures of physicochemical interactions underlying phase separation.
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