ArticleNature2015
Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 papers.
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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.
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Who cites it
213 citing papers in PubMed, 376 citations in OpenAlex.
- Chaperone-mediated remodelling of mutant huntingtin.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Hsp70 diversification and repurposing across the tree of life: Lessons from the evolutionary and mechanistic trajectory of the Hsp70-Hsp110 chaperone system.The FEBS journal · 2026Review
- ER-to-Golgi transport machinery promotes the excessive cargo-triggered unfolded protein response in C. elegans.PLoS genetics · 2026Article
- Mixed-class J-domain protein scaffolds promote expanded aggregate handling and multivalent Hsp70 engagement during functional disaggregase assembly.FEBS letters · 2026Article
- Wiring of cellular proteostasis by J-domain proteins.Cell stress & chaperones · 2026Review
- Small bites for big problems: stepwise aggregate degradation by autophagy.Biochemical Society transactions · 2026Review
- The ALS-associated E425K mutation uncouples DNAJC7 from the Hsp70 chaperone cycle.The FEBS journal · 2026Article
- Small molecules modulate the biomolecular condensates and liquid‒liquid phase separation.Acta pharmaceutica Sinica. B · 2026Review
- Functions of J-domain proteins in mitochondrial protein biogenesis.Protein science : a publication of the Protein Society · 2026Review
- HSP-1-specific nanobodies alter chaperone function in vitro and in vivo.The Journal of biological chemistry · 2026Article
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- Origin of class B J-domain proteins involved in amyloid transactions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Contrasting roles of autophagy in cellular prion infection.Autophagy · 2025Article
- Structural polymorphism of α-synuclein fibrils alters the pathway of Hsc70-mediated disaggregation.The EMBO journal · 2025Article
- Competing chaperone pathways in α-synuclein disaggregation and aggregation dynamics.Protein science : a publication of the Protein Society · 2025Article
- A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy.Nature cell biology · 2025Article
- How does protein aggregate structure affect mechanisms of disaggregation?Biochemical Society transactions · 2025Review
- Article
- The Role of α-Synuclein-DNAJB6b Coaggregation in Amyloid Suppression.ACS chemical neuroscience · 2025Article
- Proteome-wide determinants of co-translational chaperone binding in bacteria.Nature communications · 2025Article
153 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states. Healthy metazoan cells effectively eliminate intracellular protein aggregates, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro. This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control.
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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.