ArticleCommunications biology2022
Arg/Lys-containing IDRs are cryptic binding domains for ATP and nucleic acids that interplay to modulate LLPS.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- (Re)defining the human chromatome: an integrated meta-analysis of localization, function, abundance, physical properties, and domain composition of chromatin proteins.Nucleic acids research · 2026Pooled it
- Adenosine triphosphate as a modulator of protein interactions and stability.FEBS open bio · 2026Review
- Protein arginine methyltransferases as regulators of phase separation: implications in cancer and neurodegenerative diseases.European biophysics journal : EBJ · 2026Review
- Hierarchical Nuclear Architecture in Pre-mRNA Splicing: From IDRs to Speckles and Meshworks.International journal of molecular sciences · 2026Review
- Revealing site-specific molecular features mediating contacts of heterochromatin protein 1 α (HP1α) and the interactions with chromatin and DNA in LLPS environments.Communications biology · 2025Article
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- The Regulation of TDP-43 Structure and Phase Transitions: A Review.The protein journal · 2025Review
- Liquid-liquid phase separation in cell physiology and cancer biology: recent advances and therapeutic implications.Frontiers in oncology · 2025Review
- Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Mechanistic Insights into RNA Oligonucleotide-Mediated Inhibition of TDP-43 Aggregation.Journal of the American Chemical Society · 2024Article
- In the Beginning: Let Hydration Be Coded in Proteins for Manifestation and Modulation by Salts and Adenosine Triphosphate.International journal of molecular sciences · 2024Review
- Molecular Mechanisms of Phase Separation and Amyloidosis of ALS/FTD-linked FUS and TDP-43.Aging and disease · 2024Review
- Biomolecular condensates and disease pathogenesis.Science China. Life sciences · 2024Review
- Adenosine Triphosphate: The Primordial Molecule That Controls Protein Homeostasis and Shapes the Genome-Proteome Interface.Biomolecules · 2024Review
- Advanced imaging techniques for studying protein phase separation in living cells and at single-molecule level.Current opinion in chemical biology · 2023Review
- Article
- Article
- ATP and nucleic acids competitively modulate LLPS of the SARS-CoV2 nucleocapsid protein.Communications biology · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most membrane-less organelles (MLOs) formed by LLPS contain both nucleic acids and IDR-rich proteins. Currently while IDRs are well-recognized to drive LLPS, nucleic acids are thought to exert non-specific electrostatic/salt effects. TDP-43 functions by binding RNA/ssDNA and its LLPS was characterized without nucleic acids to be driven mainly by PLD-oligomerization, which may further transit into aggregation characteristic of various neurodegenerative diseases. Here by NMR, we discovered unexpectedly for TDP-43 PLD: 1) ssDNAs drive and then dissolve LLPS by multivalently and specifically binding Arg/Lys. 2) LLPS is driven by nucleic-acid-binding coupled with PLD-oligomerization. 3) ATP and nucleic acids universally interplay in modulating LLPS by competing for binding Arg/Lys. However, the unique hydrophobic region within PLD renders LLPS to exaggerate into aggregation. The study not only unveils the first residue-resolution mechanism of the nucleic-acid-driven LLPS of TDP-43 PLD, but also decodes a general principle that not just TDP-43 PLD, all Arg/Lys-containing IDRs are cryptic nucleic-acid-binding domains that may phase separate upon binding nucleic acids. Strikingly, ATP shares a common mechanism with nucleic acids in binding IDRs, thus emerging as a universal mediator for interactions between IDRs and nucleic acids, which may underlie previously-unrecognized roles of ATP at mM in physiology and pathology.
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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.