ArticleProceedings of the National Academy of Sciences of the United States of America2014
Deep classification of a large cryo-EM dataset defines the conformational landscape of the 26S proteasome.
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 118 papers, 1 of them a synthesis that pooled it.
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Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Substrate-interacting pore loops of two ATPase subunits determine the degradation efficiency of the 26S proteasome.Nature communications · 2026Article
- Article
- Within and beyond the boundaries of proteasomal assembly: PSMD9 chaperone as a multifunctional protein.Essays in biochemistry · 2025Review
- Article
- Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome.Nature communications · 2025Article
- The deubiquitinase Rpn11 functions as an allosteric ubiquitin sensor to promote substrate engagement by the 26S proteasome.Cell reports · 2025Article
- Proteasome dynamics in response to metabolic changes.Frontiers in cell and developmental biology · 2025Review
- Hepatitis B virus infection disrupts homologous recombination in hepatocellular carcinoma by stabilizing resection inhibitor ADRM1.The Journal of clinical investigation · 2023Article
- Molecular mechanism for activation of the 26S proteasome by ZFAND5.Molecular cell · 2023Article
- Wiggle and Shake: Managing and Exploiting Conformational Dynamics during Proteasome Biogenesis.Biomolecules · 2023Review
- FAT10 and NUB1L cooperate to activate the 26S proteasome.Life science alliance · 2023Article
- 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
- Frozen in time: analyzing molecular dynamics with time-resolved cryo-EM.Structure (London, England : 1993) · 2023Review
- Ubiquitin modulates 26Science advances · 2022Article
- Structure of the reduced microsporidian proteasome bound by PI31-like peptides in dormant spores.Nature communications · 2022Article
- Proteasome substrate receptors and their therapeutic potential.Trends in biochemical sciences · 2022Review
- Assembly checkpoint of the proteasome regulatory particle is activated by coordinated actions of proteasomal ATPase chaperones.Cell reports · 2022Article
- Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.Nature communications · 2022Article
- Cryo-EM structure of the plant 26S proteasome.Plant communications · 2022Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 26S proteasome is a 2.5 MDa molecular machine that executes the degradation of substrates of the ubiquitin-proteasome pathway. The molecular architecture of the 26S proteasome was recently established by cryo-EM approaches. For a detailed understanding of the sequence of events from the initial binding of polyubiquitylated substrates to the translocation into the proteolytic core complex, it is necessary to move beyond static structures and characterize the conformational landscape of the 26S proteasome. To this end we have subjected a large cryo-EM dataset acquired in the presence of ATP and ATP-γS to a deep classification procedure, which deconvolutes coexisting conformational states. Highly variable regions, such as the density assigned to the largest subunit, Rpn1, are now well resolved and rendered interpretable. Our analysis reveals the existence of three major conformations: in addition to the previously described ATP-hydrolyzing (ATPh) and ATP-γS conformations, an intermediate state has been found. Its AAA-ATPase module adopts essentially the same topology that is observed in the ATPh conformation, whereas the lid is more similar to the ATP-γS bound state. Based on the conformational ensemble of the 26S proteasome in solution, we propose a mechanistic model for substrate recognition, commitment, deubiquitylation, and translocation into the core particle.
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