ReviewJournal of molecular biology2016
Mechanistic and Structural Insights into the Prion-Disaggregase Activity of Hsp104.
Review in Journal of molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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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
64 citing papers in PubMed, 105 citations in OpenAlex.
- Scouring the human Hsp70 network uncovers diverse chaperone safeguards buffering TDP-43 toxicity.bioRxiv : the preprint server for biology · 2025Article
- A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies inJournal of fungi (Basel, Switzerland) · 2025Review
- VCP regulates early tau seed amplification via specific cofactors.Molecular neurodegeneration · 2025Article
- Design principles to tailor Hsp104 therapeutics.Cell reports · 2024Article
- Decoding chaperone complexes: Insights from NMR spectroscopy.Biophysics reviews · 2024Review
- The middle domain of Hsp104 can ensure substrates are functional after processing.PLoS genetics · 2024Article
- VCP regulates early tau seed amplification via specific cofactors.Research square · 2024Article
- Design principles to tailor Hsp104 therapeutics.bioRxiv : the preprint server for biology · 2024Article
- 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
- Mechanisms tailoring the expression of heat shock proteins to proteostasis challenges.The Journal of biological chemistry · 2022Review
- AAA+ proteins: one motor, multiple ways to work.Biochemical Society transactions · 2022Review
- Review
- The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Proteostasis Factors.Journal of neuropathology and experimental neurology · 2021Review
- Combating deleterious phase transitions in neurodegenerative disease.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Fas Apoptosis Inhibitory Molecule Blocks and Dissolves Pathological Amyloid-β Species.Frontiers in molecular neuroscience · 2021Article
- Article
- Multi-scale 3D Cryo-Correlative Microscopy for Vitrified Cells.Structure (London, England : 1993) · 2020Article
- Understanding and exploiting interactions between cellular proteostasis pathways and infectious prion proteins for therapeutic benefit.Open biology · 2020Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Hsp104 is a dynamic ring translocase and hexameric AAA+ protein found in yeast, which couples ATP hydrolysis to disassembly and reactivation of proteins trapped in soluble preamyloid oligomers, disordered protein aggregates, and stable amyloid or prion conformers. Here, we highlight advances in our structural understanding of Hsp104 and how Hsp104 deconstructs Sup35 prions. Although the atomic structure of Hsp104 hexamers remains uncertain, volumetric reconstruction of Hsp104 hexamers in ATPγS, ADP-AlFx (ATP hydrolysis transition-state mimic), and ADP via small-angle x-ray scattering has revealed a peristaltic pumping motion upon ATP hydrolysis. This pumping motion likely drives directional substrate translocation across the central Hsp104 channel. Hsp104 initially engages Sup35 prions immediately C-terminal to their cross-β structure. Directional pulling by Hsp104 then resolves N-terminal cross-β structure in a stepwise manner. First, Hsp104 fragments the prion. Second, Hsp104 unfolds cross-β structure. Third, Hsp104 releases soluble Sup35. Deletion of the Hsp104 N-terminal domain yields a hypomorphic disaggregase, Hsp104(∆N), with an altered pumping mechanism. Hsp104(∆N) fragments Sup35 prions without unfolding cross-β structure or releasing soluble Sup35. Moreover, Hsp104(∆N) activity cannot be enhanced by mutations in the middle domain that potentiate disaggregase activity. Thus, the N-terminal domain is critical for the full repertoire of Hsp104 activities.
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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.