ArticleProceedings of the National Academy of Sciences of the United States of America2021
Class-specific interactions between Sis1 J-domain protein and Hsp70 chaperone potentiate disaggregation of misfolded proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 52 citations in OpenAlex.
- Wiring of cellular proteostasis by J-domain proteins.Cell stress & chaperones · 2026Review
- Transcriptomic analysis of Rnq1 loss and prionization reveals alterations in translation pathways and energy metabolism.Scientific reports · 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
- Intracellular aggregation of the transthyretin protein is limited by Hsp70 chaperones.bioRxiv : the preprint server for biology · 2025Article
- Mechanosensor-mediated Hsp70 phosphorylation orchestrates the landscape of the heat shock response.Nature communications · 2025Article
- A universal entropic pulling force caused by binding.Nature communications · 2025Article
- Article
- How does protein aggregate structure affect mechanisms of disaggregation?Biochemical Society transactions · 2025Review
- Co-chaperones fine-tune the function of heat shock protein 70 (Hsp70), whether to fold, hold, or degrade substrates in ensuring cellular protein homeostasis.Journal of biosciences · 2025Review
- Design principles to tailor Hsp104 therapeutics.Cell reports · 2024Article
- NMR Studies on the Structure of Yeast Sis1 and the Dynamics of Its Interaction with Ssa1-EEVD.Molecules (Basel, Switzerland) · 2024Article
- Early steps of protein disaggregation by Hsp70 chaperone and class B J-domain proteins are shaped by Hsp110.eLife · 2024Article
- Misfolding and aggregation in neurodegenerative diseases: protein quality control machinery as potential therapeutic clearance pathways.Cell communication and signaling : CCS · 2024Review
- Comparative genomic analysis reveals expansion of the DnaJ gene family in Lagerstroemia indica and its members response to salt stress.Genetica · 2024Article
- Design principles to tailor Hsp104 therapeutics.bioRxiv : the preprint server for biology · 2024Article
- Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative Stress Tolerance through Mediating Antioxidant Systems and Transcriptional Regulation.Antioxidants (Basel, Switzerland) · 2024Article
- J-domain proteins: From molecular mechanisms to diseases.Cell stress & chaperones · 2024Article
- The HSP40 family chaperone isoform DNAJB6b prevents neuronal cells from tau aggregation.BMC biology · 2023Article
- Formation of Transient Protein Aggregate-like Centers Is a General Strategy Postponing Degradation of Misfolded Intermediates.International journal of molecular sciences · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein homeostasis is constantly being challenged with protein misfolding that leads to aggregation. Hsp70 is one of the versatile chaperones that interact with misfolded proteins and actively support their folding. Multifunctional Hsp70s are harnessed to specific roles by J-domain proteins (JDPs, also known as Hsp40s). Interaction with the J-domain of these cochaperones stimulates ATP hydrolysis in Hsp70, which stabilizes substrate binding. In eukaryotes, two classes of JDPs, Class A and Class B, engage Hsp70 in the reactivation of aggregated proteins. In most species, excluding metazoans, protein recovery also relies on an Hsp100 disaggregase. Although intensely studied, many mechanistic details of how the two JDP classes regulate protein disaggregation are still unknown. Here, we explore functional differences between the yeast Class A (Ydj1) and Class B (Sis1) JDPs at the individual stages of protein disaggregation. With real-time biochemical tools, we show that Ydj1 alone is superior to Sis1 in aggregate binding, yet it is Sis1 that recruits more Ssa1 molecules to the substrate. This advantage of Sis1 depends on its ability to bind to the EEVD motif of Hsp70, a quality specific to most of Class B JDPs. This second interaction also conditions the Hsp70-induced aggregate modification that boosts its subsequent dissolution by the Hsp104 disaggregase. Our results suggest that the Sis1-mediated chaperone assembly at the aggregate surface potentiates the entropic pulling, driven polypeptide disentanglement, while Ydj1 binding favors the refolding of the solubilized proteins. Such subspecialization of the JDPs across protein reactivation improves the robustness and efficiency of the disaggregation machinery.
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