ArticleThe Journal of biological chemistry2013
The ATP costs and time required to degrade ubiquitinated proteins by the 26 S proteasome.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 141 citations in OpenAlex.
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Evolution of N-terminal mechanical lability as a determinant for Type III secretion.Protein science : a publication of the Protein Society · 2026Article
- Molecular basis of ubiquitin-independent recognition and degradation of ODC/Antizyme by the 26S proteasome.bioRxiv : the preprint server for biology · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Energy-precision trade-off in mitotic oscillators revealed by ATP modulation in artificial cells.bioRxiv : the preprint server for biology · 2026Article
- A Type III secretion system effector evolved to be mechanically labile and initiate unfolding from the N-terminus.bioRxiv : the preprint server for biology · 2026Article
- Thermodynamically consistent, reduced models of gene regulatory networks.Royal Society open science · 2025Article
- Selective clearance of aberrant membrane proteins by TORC1-mediated micro-ER-phagy.Cell reports · 2025Article
- Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy.Autophagy · 2025Article
- Proteasome dynamics in response to metabolic changes.Frontiers in cell and developmental biology · 2025Review
- A synthetic protein-level neural network in mammalian cells.Science (New York, N.Y.) · 2024Article
- Rapid adaptation of cellular metabolic rate to the MicroRNA complements of mammals and its relevance to the evolution of endothermy.iScience · 2024Article
- The proteasome as a drug target for treatment of parasitic diseases.Advances in parasitology · 2024Review
- How much (ATP) does it cost to build a trypanosome? A theoretical study on the quantity of ATP needed to maintain and duplicate a bloodstream-form Trypanosoma brucei cell.PLoS pathogens · 2023Article
- Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity.Aging and disease · 2023Review
- The Ubiquitin-26S Proteasome Pathway and Its Role in the Ripening of Fleshy Fruits.International journal of molecular sciences · 2023Review
- The molecular basis of cereal grain proteostasis.Essays in biochemistry · 2022Review
- Review
- Impact of MnTBAP and Baricitinib Treatment on Hutchinson-Gilford Progeria Fibroblasts.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Translational suppression via IFG-1/eIF4G inhibits stress-induced RNA alternative splicing in Caenorhabditis elegans.Genetics · 2022Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The degradation of ubiquitinated proteins by 26 S proteasomes requires ATP hydrolysis. To investigate if the six proteasomal ATPases function independently or in a cyclic manner, as proposed recently, we used yeast mutants that prevent ATP binding to Rpt3, Rpt5, or Rpt6. Although proteasomes contain six ATPase subunits, each of these single mutations caused a 66% reduction in basal ATP hydrolysis, and each blocked completely the 2-3-fold stimulation of ATPase activity induced by ubiquitinated substrates. Therefore, the ATPase subunits must function in a ordered manner, in which each is required for the stimulation of ATPase activity by substrates. Although ATP is essential for multiple steps in proteasome function, when the rate of ATP hydrolysis was reduced incrementally, the degradation of Ub5-DHFR (where Ub is ubiquitin and DHFR is dihydrofolate reductase) decreased exactly in parallel. This direct proportionality implies that a specific number of ATPs is consumed in degrading a ubiquitinated protein. When the ubiquitinated DHFR was more tightly folded (upon addition of the ligand folate), the rate of ATP hydrolysis was unchanged, but the time to degrade a Ub5-DHFR molecule (∼13 s) and the energy expenditure (50-80 ATPs/Ub5-DHFR) both increased by 2-fold. With a mutation in the ATPase C terminus that reduced gate opening into the 20 S proteasome, the energy costs and time required for conjugate degradation also increased. Thus, different ubiquitin conjugates activate similarly the ATPase subunit cycle that drives proteolysis, but polypeptide structure determines the time required for degradation and thus the energy cost.
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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.