ReviewThe Journal of biological chemistry2022
Recent structural insights into the mechanism of ClpP protease regulation by AAA+ chaperones and small molecules.
Review in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 63 citations in OpenAlex.
- Article
- Small molecule activators of the mitochondrial protease ClpP induce senescence in triple-negative breast cancer cells and sensitize cells to the Bcl-2 inhibitor venetoclax.Cell death & disease · 2026Article
- Structure-function analysis of the bacterial ClpE-ClpP AAA+ protease.The Journal of biological chemistry · 2026Article
- Mode of action guided metagenomic natural product discovery reveals convergent evolution of a ClpP-targeting motif.Nature communications · 2026Article
- YdbL directly modulates YdbH-YnbE bridge formation to maintainbioRxiv : the preprint server for biology · 2026Article
- Discovery of a pyridine-piperazine-based small molecule that enhances the activity of peptidase neurolysin.The Journal of pharmacology and experimental therapeutics · 2026Article
- Bioinformatic evaluation of ClpP as a vaccine target in Streptococcus pneumoniae.Biotechnology letters · 2026Article
- Structural and mechanistic insights into caseinolytic protease inhibition for antimicrobial development against Pseudomonas plecoglossicida.PLoS pathogens · 2026Article
- Cryo-EM structures of human ClpXP reveal mechanisms of assembly and proteolytic activation.Nature communications · 2026Article
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 2026Review
- Polydatin as a natural ClpP modulator for combating methicillin-resistantFrontiers in cellular and infection microbiology · 2026Article
- Development and evaluation of mitochondria-targeted caseinolytic protease (ClpP) agonist chemical probes in in vitro breast cancer models.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Small Molecule Activators of the Mitochondrial Protease ClpP Induce Senescence in Triple-Negative Breast Cancer Cells and Sensitize Cells to the Bcl-2 Inhibitor Venetoclax.Research square · 2025Article
- Natural products influence bacteriophage infectivity.Natural product reports · 2025Review
- Structure of the central Staphylococcus aureus AAA+ protease MecA/ClpC/ClpP.Communications biology · 2025Article
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- CLIPPERs - Clip the right protein - a new tool for targeted proteolysis in bacteria.EMBO reports · 2025Article
- Recent Advances in the Structural Studies of the Proteolytic ClpP/ClpX Molecular Machine.Biomolecules · 2025Review
- Degradation of Nonribosomal Peptide Synthetase Megasynthetases SrfAA and SrfAB by Acyldepsipeptide-Activated ClpP in Bacillus Subtilis.Chembiochem : a European journal of chemical biology · 2025Article
- Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
ClpP is a highly conserved serine protease that is a critical enzyme in maintaining protein homeostasis and is an important drug target in pathogenic bacteria and various cancers. In its functional form, ClpP is a self-compartmentalizing protease composed of two stacked heptameric rings that allow protein degradation to occur within the catalytic chamber. ATPase chaperones such as ClpX and ClpA are hexameric ATPases that form larger complexes with ClpP and are responsible for the selection and unfolding of protein substrates prior to their degradation by ClpP. Although individual structures of ClpP and ATPase chaperones have offered mechanistic insights into their function and regulation, their structures together as a complex have only been recently determined to high resolution. Here, we discuss the cryoelectron microscopy structures of ClpP-ATPase complexes and describe findings previously inaccessible from individual Clp structures, including how a hexameric ATPase and a tetradecameric ClpP protease work together in a functional complex. We then discuss the consensus mechanism for substrate unfolding and translocation derived from these structures, consider alternative mechanisms, and present their strengths and limitations. Finally, new insights into the allosteric control of ClpP gained from studies using small molecules and gain or loss-of-function mutations are explored. Overall, this review aims to underscore the multilayered regulation of ClpP that may present novel ideas for structure-based drug design.
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