ArticleThe Journal of biological chemistry2013
Slippery substrates impair ATP-dependent protease function by slowing unfolding.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Modeling liquid-liquid phase separation and its impact on proteasomal substrate degradation.Computational and structural biotechnology journal · 2025Article
- How the double-ring ClpAP protease motor grips the substrate to unfold and degrade stable proteins.The Journal of biological chemistry · 2024Article
- Toxin-based screening of C-terminal tags inbioRxiv : the preprint server for biology · 2024Article
- AAA+ protease-adaptor structures reveal altered conformations and ring specialization.Nature structural & molecular biology · 2022Article
- Single molecule microscopy reveals diverse actions of substrate sequences that impair ClpX AAA+ ATPase function.The Journal of biological chemistry · 2022Article
- Structure and function of ClpXP, a AAA+ proteolytic machine powered by probabilistic ATP hydrolysis.Critical reviews in biochemistry and molecular biology · 2022Review
- Cell-to-cell transmission of C9orf72 poly-(Gly-Ala) triggers key features of ALS/FTD.The EMBO journal · 2020Article
- Article
- Non-Proteasomal UbL-UbA Family of Proteins in Neurodegeneration.International journal of molecular sciences · 2019Review
- Regulated Proteolysis in Bacteria.Annual review of biochemistry · 2018Review
- Article
- Knots can impair protein degradation by ATP-dependent proteases.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Logic of the 26S Proteasome.Cell · 2017Review
- Disordered proteinaceous machines.Chemical reviews · 2014Review
- Article
- Reply to Coffino et al.: slippery substrates impair ATP-dependent protease function by slowing unfolding.The Journal of biological chemistry · 2014Article
- Slippery substrates impair ATP-dependent protease function by slowing unfolding.The Journal of biological chemistry · 2014Article
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATP-dependent proteases are responsible for most energy-dependent protein degradation across all species. Proteases initially bind an unstructured region on a substrate and then translocate along the polypeptide chain, unfolding and degrading protein domains as they are encountered. Although this process is normally processive, resulting in the complete degradation of substrate proteins to small peptides, some substrates are released prematurely. Regions of low sequence complexity within the substrate such as the glycine-rich region (GRR) from p105 or glycine-alanine repeats (GAr) from the EBNA1 (Epstein-Barr virus nuclear antigen-1) protein, can trigger partial degradation and fragment release. Loss of processivity could be due to inability to hold on to the substrate (faster release) or inability to unfold and degrade a substrate domain (slower unfolding). I previously showed that the GRR slows domain unfolding by the proteasome (Kraut, D. A., Israeli, E., Schrader, E. K., Patil, A., Nakai, K., Nanavati, D., Inobe, T., and Matouschek, A. (2012) ACS Chem. Biol. 7, 1444-1453). In contrast, a recently published study concluded that GArs increase the rate of substrate release from ClpXP, a bacterial ATP-dependent protease (Too, P. H., Erales, J., Simen, J. D., Marjanovic, A., and Coffino, P. (2013) J. Biol. Chem. 288, 13243-13257). Here, I show that these apparently contradictory results can be reconciled through a reanalysis of the ClpXP GAr data. This reanalysis shows that, as with the proteasome, low complexity sequences in substrates slow their unfolding and degradation by ClpXP, with little effect on release rates. Thus, despite their evolutionary distance and limited sequence identity, both ClpXP and the proteasome share a common mechanism by which substrate sequences regulate the processivity of degradation.
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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.