ArticleProceedings of the National Academy of Sciences of the United States of America2012
Proteasome allostery as a population shift between interchanging conformers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
- Tetra-anionic porphyrin mimics protein-protein interactions between regulatory particles and the catalytic core, allosterically activating human 20S proteasome.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- The Evolving Landscape of Protein Allostery: From Computational and Experimental Perspectives.Journal of molecular biology · 2025Review
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- Not Just PA28γ: What We Know About the Role of PA28αβ in Carcinogenesis.Biomolecules · 2025Review
- High-resolution characterization of ex vivo AAT polymers by solution-state NMR spectroscopy.Science advances · 2025Article
- Structural basis for allosteric modulation of M. tuberculosis proteasome core particle.Nature communications · 2025Article
- Blm10-Based Compounds Add to the Knowledge of How Allosteric Modulators Influence Human 20S Proteasome.ACS chemical biology · 2025Article
- Dynamic sampling of a surveillance state enables DNA proofreading by Cas9.Cell chemical biology · 2025Article
- Changes in the hydrophobic network of the FliGiScience · 2023Article
- Minimal mechanistic component of HbYX-dependent proteasome activation that reverses impairment by neurodegenerative-associated oligomers.Communications biology · 2023Article
- AI-designed NMR spectroscopy RF pulses for fast acquisition at high and ultra-high magnetic fields.Nature communications · 2023Article
- Allosteric regulation of the 20S proteasome by the Catalytic Core Regulators (CCRs) family.Nature communications · 2023Article
- The proteasome regulator PSME4 modulates proteasome activity and antigen diversity to abrogate antitumor immunity in NSCLC.Nature cancer · 2023Article
- Electronic Circular Dichroism Detects Conformational Changes Associated with Proteasome Gating Confirmed Using AFM Imaging.Biomolecules · 2023Article
- Minimal mechanistic component of HbYX-dependent proteasome activation.Research square · 2023Article
- Identification of core allosteric sites through temperature- and nucleus-invariant chemical shift covariance.Biophysical journal · 2022Article
- Peptidomimetics Based onBiomolecules · 2022Article
- Ligand-induced structural transitions combined with paramagnetic ions facilitate unambiguous NMR assignments of methyl groups in large proteins.Journal of biomolecular NMR · 2022Article
- Allostery Modulates Interactions between Proteasome Core Particles and Regulatory Particles.Biomolecules · 2022Review
- Modulation of the 20S Proteasome Activity by Porphyrin Derivatives Is Steered through Their Charge Distribution.Biomolecules · 2022Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors.
Funding
Abstract
Protein degradation plays a critical role in cellular homeostasis, in regulating the cell cycle, and in the generation of peptides that are used in the immune response. The 20S proteasome core particle (CP), a barrel-like structure consisting of four heptameric protein rings stacked axially on top of each other, is central to this process. CP function is controlled by activator complexes that bind 75 Å away from sites catalyzing proteolysis, and biochemical data are consistent with an allosteric mechanism by which binding is communicated to distal active sites. However, little structural evidence has emerged from the high-resolution images of the CP. Using methyl TROSY NMR spectroscopy, we demonstrate that in solution, the CP interconverts between multiple conformations whose relative populations are shifted on binding of the 11S activator or mutation of residues that contact activators. These conformers differ in contiguous regions of structure that connect activator binding to the CP active sites, and changes in their populations lead to differences in substrate proteolysis patterns. Moreover, various active site modifications result in conformational changes to the activator binding site by modulating the relative populations of these same CP conformers. This distribution is also affected by the binding of a small-molecule allosteric inhibitor of proteolysis, chloroquine, suggesting an important avenue in the development of therapeutics for proteasome inhibition.
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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.