ArticleJournal of the American Chemical Society2023
Mass Spectrometry of RNA-Binding Proteins during Liquid-Liquid Phase Separation Reveals Distinct Assembly Mechanisms and Droplet Architectures.
Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Folded domains impose structural heterogeneity and attenuated dynamics in biomolecular condensates.Nature communications · 2026Article
- Controlling intermolecular base pairing in Drosophila germ granules by mRNA folding and its implications in fly development.Nature communications · 2025Article
- Uncovering protein conformational dynamics within two-component viral biomolecular condensates.Protein science : a publication of the Protein Society · 2025Article
- The Regulation of TDP-43 Structure and Phase Transitions: A Review.The protein journal · 2025Review
- 8q24 derived ZNF252P promotes tumorigenesis by driving phase separation to activate c-Myc mediated feedback loop.Nature communications · 2025Article
- Native Mass Spectrometry Captures the Conformational Plasticity of Proteins with Low-Complexity Domains.JACS Au · 2025Article
- Phase separation in DNA double-strand break response.Nucleus (Austin, Tex.) · 2024Review
- Biomolecular condensates and disease pathogenesis.Science China. Life sciences · 2024Review
- HDX-MS finds that partial unfolding with sequential domain activation controls condensation of a cellular stress marker.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Ensemble structure of the N-terminal domain (1-267) of FUS in a biomolecular condensate.Biophysical journal · 2024Article
- Advances in mass spectrometry to unravel the structure and function of protein condensates.Nature protocols · 2023Review
- Monitoring Disassembly and Cargo Release of Phase-Separated Peptide Coacervates with Native Mass Spectrometry.Analytical chemistry · 2023Article
- Liquid-Liquid Phase Separation Primes Spider Silk Proteins for Fiber Formation via a Conditional Sticker Domain.Nano letters · 2023Article
- Ion Mobility Mass Spectrometry Unveils Global Protein Conformations in Response to Conditions that Promote and Reverse Liquid-Liquid Phase Separation.Journal of the American Chemical Society · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liquid-liquid phase separation (LLPS) of heterogeneous ribonucleoproteins (hnRNPs) drives the formation of membraneless organelles, but structural information about their assembled states is still lacking. Here, we address this challenge through a combination of protein engineering, native ion mobility mass spectrometry, and molecular dynamics simulations. We used an LLPS-compatible spider silk domain and pH changes to control the self-assembly of the hnRNPs FUS, TDP-43, and hCPEB3, which are implicated in neurodegeneration, cancer, and memory storage. By releasing the proteins inside the mass spectrometer from their native assemblies, we could monitor conformational changes associated with liquid-liquid phase separation. We find that FUS monomers undergo an unfolded-to-globular transition, whereas TDP-43 oligomerizes into partially disordered dimers and trimers. hCPEB3, on the other hand, remains fully disordered with a preference for fibrillar aggregation over LLPS. The divergent assembly mechanisms revealed by ion mobility mass spectrometry of soluble protein species that exist under LLPS conditions suggest structurally distinct complexes inside liquid droplets that may impact RNA processing and translation depending on biological context.
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