MdfA is a novel ClpC adaptor protein that functions in the developing

Massoni, Shawn C; Evans, Nicola J; Hantke, Ingo; Fenton, Colleen; Torpey, James H; Collins, Katherine M; Krysztofinska, Ewelina M; Muench, Janina H; Thapaliya, Arjun; Martínez-Lumbreras, Santiago; Hart Ferrell, Sé; Slater, Celia; Wang, Xinyue; Fekade, Ruth; Obwar, Sandra; Yin, Siyu; Vazquez, Alishba; Prior, Christopher B; Turgay, Kürşad; Isaacson, Rivka L; Camp, Amy H

Abstract

Bacterial protein degradation machinery consists of chaperone-protease complexes that play vital roles in bacterial growth and development and have sparked interest as novel antimicrobial targets. ClpC-ClpP (ClpCP) is one such chaperone-protease complex, recruited by adaptors to specific functions in the model bacterium and other Gram-positive bacteria, including the pathogens and Here we have identified a new ClpCP adaptor protein, MdfA (metabolic differentiation factor A; formerly YjbA), in a genetic screen for factors that help drive toward metabolic dormancy during spore formation. A knockout of stimulates gene expression in the developing spore, while aberrant expression of during vegetative growth is toxic. MdfA binds directly to ClpC to induce its oligomerization and ATPase activity, and this interaction is required for the in vivo effects of Finally, a cocrystal structure reveals that MdfA binds to the ClpC N-terminal domain at a location analogous to that on the ClpC1 protein where bactericidal cyclic peptides bind. Altogether, our data and that of an accompanying study by Riley and colleagues support a model in which MdfA induces ClpCP-mediated degradation of metabolic enzymes in the developing spore, helping drive it toward metabolic dormancy. [Abstract copyright: © 2025 Massoni et al.; Published by Cold Spring Harbor Laboratory Press.]

Citation

Massoni, S. C., Evans, N. J., Hantke, I., Fenton, C., Torpey, J. H., Collins, K. M., Krysztofinska, E. M., Muench, J. H., Thapaliya, A., Martínez-Lumbreras, S., Hart Ferrell, S., Slater, C., Wang, X., Fekade, R., Obwar, S., Yin, S., Vazquez, A., Prior, C. B., Turgay, K., Isaacson, R. L., & Camp, A. H. (2025). MdfA is a novel ClpC adaptor protein that functions in the developing. Genes & Development, 39, 510-523. https://doi.org/10.1101/gad.352498.124

• Journal Article Type: Article
• Acceptance Date: Feb 13, 2025
• Online Publication Date: Mar 14, 2025
• Publication Date: 2025
• Deposit Date: Apr 2, 2025
• Publicly Available Date: Sep 15, 2025
• Journal: Genes & development
• Print ISSN: 0890-9369
• Electronic ISSN: 1549-5477
• Publisher: Cold Spring Harbor Laboratory Press
• Peer Reviewed: Peer Reviewed
• Volume: 39
• Pages: 510-523
• DOI: https://doi.org/10.1101/gad.352498.124
• Keywords: YjbA, protein degradation, X-ray crystallography, ClpCP, MdfA, sporulation, Bacillus subtilis, adaptor, AAA+ proteases, ClpC
• Public URL: https://durham-repository.worktribe.com/output/3745671