ArticleProceedings of the National Academy of Sciences of the United States of America2014
Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
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- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Plasticity in the structure and assembly of proteasomes.The Journal of biological chemistry · 2026Review
- Targeting the PSMD14-BCKDK pathway overcomes immune suppression and enhances CAR-NK infiltration in glioblastoma.Cell death and differentiation · 2026Article
- Structural insights into the ubiquitin-independent midnolin-proteasome pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The ZnDevelopmental cell · 2024Article
- Slippery sequences stall the 26S proteasome at multiple points along the translocation pathway.Protein science : a publication of the Protein Society · 2024Article
- Person-specific differences in ubiquitin-proteasome mediated proteostasis in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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- Discovery of a non-covalent ligand for Rpn-13, a therapeutic target for hematological cancers.Bioorganic & medicinal chemistry letters · 2023Article
- Wiggle and Shake: Managing and Exploiting Conformational Dynamics during Proteasome Biogenesis.Biomolecules · 2023Review
- Emerging functions of pseudoenzymes.The Biochemical journal · 2023Review
- To Kill or to Be Killed: How Does the Battle between the UPS and Autophagy Maintain the Intracellular Homeostasis in Eukaryotes?International journal of molecular sciences · 2023Review
- High-Throughput Assay for Characterizing Rpn11 Deubiquitinase Activity.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Ubiquitin modulates 26Science advances · 2022Article
- The Ubiquitin-Proteasome System (UPS) and Viral Infection in Plants.Plants (Basel, Switzerland) · 2022Review
- POH1/Rpn11/PSMD14: a journey from basic research in fission yeast to a prognostic marker and a druggable target in cancer cells.British journal of cancer · 2022Review
- Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.Biomolecules · 2022Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ATP-dependent degradation of polyubiquitylated proteins by the 26S proteasome is essential for the maintenance of proteome stability and the regulation of a plethora of cellular processes. Degradation of substrates is preceded by the removal of polyubiquitin moieties through the isopeptidase activity of the subunit Rpn11. Here we describe three crystal structures of the heterodimer of the Mpr1-Pad1-N-terminal domains of Rpn8 and Rpn11, crystallized as a fusion protein in complex with a nanobody. This fusion protein exhibits modest deubiquitylation activity toward a model substrate. Full activation requires incorporation of Rpn11 into the 26S proteasome and is dependent on ATP hydrolysis, suggesting that substrate processing and polyubiquitin removal are coupled. Based on our structures, we propose that premature activation is prevented by the combined effects of low intrinsic ubiquitin affinity, an insertion segment acting as a physical barrier across the substrate access channel, and a conformationally unstable catalytic loop in Rpn11. The docking of the structure into the proteasome EM density revealed contacts of Rpn11 with ATPase subunits, which likely stabilize the active conformation and boost the affinity for the proximal ubiquitin moiety. The narrow space around the Rpn11 active site at the entrance to the ATPase ring pore is likely to prevent erroneous deubiquitylation of folded proteins.
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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.