ArticleBMC biochemistry2011
Assembly and proteolytic processing of mycobacterial ClpP1 and ClpP2.
Article in BMC biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- Mode of action guided metagenomic natural product discovery reveals convergent evolution of a ClpP-targeting motif.Nature communications · 2026Article
- Host-Directed Therapies Based on Protease Inhibitors to ControlMicroorganisms · 2025Review
- ClpS Directs Degradation of N-Degron Substrates With Primary Destabilizing Residues in Mycolicibacterium smegmatis.Molecular microbiology · 2025Article
- TamGen: drug design with target-aware molecule generation through a chemical language model.Nature communications · 2024Article
- ApoE Mimetic Peptide COG1410 KillsAntibiotics (Basel, Switzerland) · 2024Article
- ClpC2 protects mycobacteria against a natural antibiotic targeting ClpC1-dependent protein degradation.Communications biology · 2023Article
- Recent structural insights into the mechanism of ClpP protease regulation by AAA+ chaperones and small molecules.The Journal of biological chemistry · 2022Review
- Structural determinants of regulated proteolysis in pathogenic bacteria by ClpP and the proteasome.Current opinion in structural biology · 2021Review
- An allosteric switch regulatesProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis.Scientific reports · 2019Article
- Mechanism of the allosteric activation of the ClpP protease machinery by substrates and active-site inhibitors.Science advances · 2019Article
- Initial Characterization of the Two ClpP Paralogs ofJournal of bacteriology · 2019Article
- Perrault syndrome type 3 caused by diverse molecular defects in CLPP.Scientific reports · 2018Article
- AAA+ Machines of Protein Destruction in Mycobacteria.Frontiers in molecular biosciences · 2017Review
- Two ways to skin a cat: acyldepsipeptides antibiotics can kill bacteria through activation or inhibition of ClpP activity.Molecular microbiology · 2016Article
- Acyldepsipeptide antibiotics kill mycobacteria by preventing the physiological functions of the ClpP1P2 protease.Molecular microbiology · 2016Article
- Structure and Functional Properties of the Active Form of the Proteolytic Complex, ClpP1P2, from Mycobacterium tuberculosis.The Journal of biological chemistry · 2016Article
- The Mycobacterium tuberculosis ClpP1P2 Protease Interacts Asymmetrically with Its ATPase Partners ClpX and ClpC1.PloS one · 2015Article
- Substrate delivery by the AAA+ ClpX and ClpC1 unfoldases activates the mycobacterial ClpP1P2 peptidase.Molecular microbiology · 2014Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCaseinolytic proteases (ClpPs) are barrel-shaped self-compartmentalized peptidases involved in eliminating damaged or short-lived regulatory proteins. The Mycobacterium tuberculosis (MTB) genome contains two genes coding for putative ClpPs, ClpP1 and ClpP2 respectively, that are likely to play a role in the virulence of the bacterium.
resultsWe report the first biochemical characterization of ClpP1 and ClpP2 peptidases from MTB. Both proteins were produced and purified in Escherichia coli. Use of fluorogenic model peptides of diverse specificities failed to show peptidase activity with recombinant mycobacterial ClpP1 or ClpP2. However, we found that ClpP1 had a proteolytic activity responsible for its own cleavage after the Arg8 residue and cleavage of ClpP2 after the Ala12 residue. In addition, we showed that the absence of any peptidase activity toward model peptides was not due to an obstruction of the entry pore by the N-terminal flexible extremity of the proteins, nor to an absolute requirement for the ClpX or ClpC ATPase complex. Finally, we also found that removing the putative propeptides of ClpP1 and ClpP2 did not result in cleavage of model peptides. We have also shown that recombinant ClpP1 and ClpP2 do not assemble in the conventional functional tetradecameric form but in lower order oligomeric species ranging from monomers to heptamers. The concomitant presence of both ClpP1 and ClpP2 did not result in tetradecameric assembly. Deleting the amino-terminal extremity of ClpP1 and ClpP2 (the putative propeptide or entry gate) promoted the assembly in higher order oligomeric species, suggesting that the flexible N-terminal extremity of mycobacterial ClpPs participated in the destabilization of interaction between heptamers.
conclusionDespite the conservation of a Ser protease catalytic triad in their primary sequences, mycobacterial ClpP1 and ClpP2 do not have conventional peptidase activity toward peptide models and display an unusual mechanism of self-assembly. Therefore, the mechanism underlying their peptidase and proteolytic activities might differ from that of other ClpP proteolytic complexes.
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