ArticleThe Journal of biological chemistry2024
Fluorescent protein tagging promotes phase separation and alters the aggregation pathway of huntingtin exon-1.
Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Probing biomolecular condensates with a minimally perturbative experimental readout framework.The Biochemical journal · 2026Review
- Valosin-containing protein counteracts ATP-driven dissolution of FUS condensates through its ATPase activity in vitro.FEBS letters · 2026Article
- The Effect of Protein Tagging on Aggregation and Phase Separation.Journal of cellular biochemistry · 2026Review
- Prion Protein-Derived Cell-Penetrating Peptide Inhibits Type II Diabetes-Associated Islet Amyloid Polypeptide Aggregation and Cytotoxicity.Biochemistry · 2026Article
- GFP-free live neuron quantitative imaging reveals compartmentalization and growth dynamics of polyQ aggregates.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Fluorescent protein and peptide tags alter condensate formation and dynamics in vivo and in vitro.EMBO reports · 2026Article
- Surface-modified protein crowders influence mutant huntingtin exon 1 aggregation via crowding effects, crowder association, and crowder solution stability.Protein science : a publication of the Protein Society · 2025Article
- Biomolecular condensates: molecular structure, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and neurodegenerative diseases.Journal of Huntington's disease · 2025Review
- Water-detected NMR allows dynamic observations of repeat-expansion RNA condensates.Nature chemistry · 2025Article
- Protofibril Binding Peptides Recognize and Inhibit Huntingtin Amyloid FormationbioRxiv : the preprint server for biology · 2025Article
- Liquid-Liquid Phase Separation from the Viewpoint of Molecular Crowding Environment: A Raman Imaging Study.The journal of physical chemistry. B · 2025Review
- Transient Interdomain Interactions Modulate the Monomeric Structural Ensemble and Self-Assembly of Huntingtin Exon 1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- LLPS REDIFINE allows the biophysical characterization of multicomponent condensates without tags or labels.Nature communications · 2025Article
- Strategic Modulation of Polarity and Viscosity Sensitivity of Bimane Molecular Rotor-Based Fluorophores for Imaging α-Synuclein.Journal of the American Chemical Society · 2025Article
- Intracellular protein editing enables incorporation of noncanonical residues in endogenous proteins.Science (New York, N.Y.) · 2025Article
- The dark side of fluorescent protein tagging-the impact of protein tags on biomolecular condensation.Molecular biology of the cell · 2025Article
- A tunable affinity fusion tag for protein self-assembly.bioRxiv : the preprint server for biology · 2025Article
- TDP43 and huntingtin Exon-1 undergo a conformationally specific interaction that strongly alters the fibril formation of both proteins.The Journal of biological chemistry · 2024Article
- Physicochemical Perspective of Biological Heterogeneity.ACS physical chemistry Au · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Fluorescent protein tags are convenient tools for tracking the aggregation states of amyloidogenic or phase separating proteins, but the effect of the tags is often not well understood. Here, we investigated the impact of a C-terminal red fluorescent protein (RFP) tag on the phase separation of huntingtin exon-1 (Httex1), an N-terminal portion of the huntingtin protein that aggregates in Huntington's disease. We found that the RFP-tagged Httex1 rapidly formed micron-sized, phase separated states in the presence of a crowding agent. The formed structures had a rounded appearance and were highly dynamic according to electron paramagnetic resonance and fluorescence recovery after photobleaching, suggesting that the phase separated state was largely liquid in nature. Remarkably, the untagged protein did not undergo any detectable liquid condensate formation under the same conditions. In addition to strongly promoting liquid-liquid phase separation, the RFP tag also facilitated fibril formation, as the tag-dependent liquid condensates rapidly underwent a liquid-to-solid transition. The rate of fibril formation under these conditions was significantly faster than that of the untagged protein. When expressed in cells, the RFP-tagged Httex1 formed larger aggregates with different antibody staining patterns compared to untagged Httex1. Collectively, these data reveal that the addition of a fluorescent protein tag significantly impacts liquid and solid phase separations of Httex1 in vitro and leads to altered aggregation in cells. Considering that the tagged Httex1 is commonly used to study the mechanisms of Httex1 misfolding and toxicity, our findings highlight the importance to validate the conclusions with untagged protein.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.