ArticleFEMS yeast research2018
Potentiating Hsp104 activity via phosphomimetic mutations in the middle domain.
Article in FEMS yeast research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- High-throughput screening approach identifies substrate-selective Hsp104 variants that counter amyloid seeding with diminished off-target effects.Molecular cell · 2026Article
- Mitochondrial respiration modulates Hsf1 activation and the heat shock response.bioRxiv : the preprint server for biology · 2026Article
- Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains.Molecular cell · 2026Article
- Crystal structures of the phosphorylation mimics of human cytosolic branched chain aminotransferase.Archives of biochemistry and biophysics · 2025Article
- Design principles to tailor Hsp104 therapeutics.Cell reports · 2024Article
- Design principles to tailor Hsp104 therapeutics.bioRxiv : the preprint server for biology · 2024Article
- Crosstalk between protein post-translational modifications and phase separation.Cell communication and signaling : CCS · 2024Review
- CRISPR screen for protein inclusion formation uncovers a role for SRRD in the regulation of intermediate filament dynamics and aggresome assembly.PLoS genetics · 2024Article
- Nuclear-import receptors as gatekeepers of pathological phase transitions in ALS/FTD.Molecular neurodegeneration · 2024Review
- Solid-to-liquid phase transition in the dissolution of cytosolic misfolded-protein aggregates.iScience · 2023Article
- Tuning Hsp104 specificity to selectively detoxify α-synuclein.Molecular cell · 2023Article
- Hsp104 N-terminal domain interaction with substrates plays a regulatory role in protein disaggregation.The FEBS journal · 2022Article
- Molecular determinants and modifiers of Matrin-3 toxicity, condensate dynamics, and droplet morphology.iScience · 2022Article
- Amyloid Fragmentation and Disaggregation in Yeast and Animals.Biomolecules · 2021Review
- Drivers of Hsp104 potentiation revealed by scanning mutagenesis of the middle domain.Protein science : a publication of the Protein Society · 2021Article
- Prion-Like Proteins in Phase Separation and Their Link to Disease.Biomolecules · 2021Review
- FUS and TDP-43 Phases in Health and Disease.Trends in biochemical sciences · 2021Review
- Combating deleterious phase transitions in neurodegenerative disease.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Article
- The clinical trial landscape in amyotrophic lateral sclerosis-Past, present, and future.Medicinal research reviews · 2020Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hsp104 is a hexameric AAA + ATPase and protein disaggregase found in yeast, which can be potentiated via mutations in its middle domain (MD) to counter toxic phase separation by TDP-43, FUS and α-synuclein connected to devastating neurodegenerative disorders. Subtle missense mutations in the Hsp104 MD can enhance activity, indicating that post-translational modification of specific MD residues might also potentiate Hsp104. Indeed, several serine and threonine residues throughout Hsp104 can be phosphorylated in vivo. Here, we introduce phosphomimetic aspartate or glutamate residues at these positions and assess Hsp104 activity. Remarkably, phosphomimetic T499D/E and S535D/E mutations in the MD enable Hsp104 to counter TDP-43, FUS and α-synuclein aggregation and toxicity in yeast, whereas T499A/V/I and S535A do not. Moreover, Hsp104T499E and Hsp104S535E exhibit enhanced ATPase activity and Hsp70-independent disaggregase activity in vitro. We suggest that phosphorylation of T499 or S535 may elicit enhanced Hsp104 disaggregase activity in a reversible and regulated manner.
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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.