ArticleMolecular microbiology2014
Substrate delivery by the AAA+ ClpX and ClpC1 unfoldases activates the mycobacterial ClpP1P2 peptidase.
Article in Molecular microbiology, 2014. 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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44 citing papers in PubMed, 79 citations in OpenAlex.
- ClpC1-dependent iron homeostasis underlies mycobacterial defense against oxygen-driven Fenton reaction during reactivation.Microbiology spectrum · 2026Article
- ClpP2 modulates ClpXP assembly to promote multiple pathogenic phenotypes inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- ClpC1-targeting peptide natural products differentially dysregulate the proteome of Mycobacterium tuberculosis.Nature communications · 2026Article
- Cryo-EM structures of human ClpXP reveal mechanisms of assembly and proteolytic activation.Nature communications · 2026Article
- Structure of the central Staphylococcus aureus AAA+ protease MecA/ClpC/ClpP.Communications biology · 2025Article
- Structure-Based Analysis of Semisynthetic Anti-TB Rufomycin Analogues.Journal of natural products · 2025Article
- Structural Insights into Bortezomib-Induced Activation of the Caseinolytic Chaperone-Protease System in Mycobacterium tuberculosis.Nature communications · 2025Article
- ClpS Directs Degradation of N-Degron Substrates With Primary Destabilizing Residues in Mycolicibacterium smegmatis.Molecular microbiology · 2025Article
- Comparison of three methods for generating the coccoid form of Helicobacter pylori and proteomic analysis.BMC microbiology · 2024Article
- Targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy.Nature communications · 2024Article
- Metabolites fromMolecules (Basel, Switzerland) · 2024Article
- Interactome Analysis Identifies MSMEI_3879 as a Substrate of Mycolicibacterium smegmatis ClpC1.Microbiology spectrum · 2023Article
- Acyldepsipeptide Antibiotics and a Bioactive Fragment Thereof Differentially PerturbACS chemical biology · 2023Article
- Bioinformatic identification of ClpI, a distinct class of Clp unfoldases in Actinomycetota.Frontiers in microbiology · 2023Article
- HEmerging microbes & infections · 2022Article
- Identification of Arginine Phosphorylation in Mycolicibacterium smegmatis.Microbiology spectrum · 2022Article
- Acyldepsipeptide Analogues: A Future Generation Antibiotics for Tuberculosis Treatment.Pharmaceutics · 2022Review
- The essentialScience advances · 2022Article
- Identification of ClpP Dual Isoform Disruption as an Antisporulation Strategy for Clostridioides difficile.Journal of bacteriology · 2022Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Mycobacterial Clp-family proteases function via collaboration of the heteromeric ClpP1P2 peptidase with a AAA+ partner, ClpX or ClpC1. These enzymes are essential for M. tuberculosis viability and are validated antibacterial drug targets, but the requirements for assembly and regulation of functional proteolytic complexes are poorly understood. Here, we report the reconstitution of protein degradation by mycobacterial Clp proteases in vitro and describe novel features of these enzymes that distinguish them from orthologues in other bacteria. Both ClpX and ClpC1 catalyse ATP-dependent unfolding and degradation of native protein substrates in conjunction with ClpP1P2, but neither mediates protein degradation with just ClpP1 or ClpP2. ClpP1P2 alone has negligible peptidase activity, but is strongly stimulated by translocation of protein substrates into ClpP1P2 by either AAA+ partner. Interestingly, our results support a model in which both binding of a AAA+ partner and protein-substrate delivery are required to stabilize active ClpP1P2. Our model has implications for therapeutically targeting ClpP1P2 in dormant M. tuberculosis, and our reconstituted systems should facilitate identification of novel Clp protease inhibitors and activators.
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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.