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

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autorschaft

  • Shawn C. Massoni
  • Nicola J. Evans
  • Ingo Hantke
  • Colleen Fenton
  • Kürsa Turgay

Organisationseinheiten

Externe Organisationen

  • Mount Holyoke College
  • King's College London
  • University of Durham
  • Max-Planck-Forschungsstelle für die Wissenschaft der Pathogene (MPUSP)
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  • Citations
    • Citation Indexes: 3
  • Mentions
    • News Mentions: 3
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Details

OriginalspracheEnglisch
Seiten (von - bis)510-523
Seitenumfang14
FachzeitschriftGenes and Development
Jahrgang39
Ausgabenummer7
PublikationsstatusVeröffentlicht - 14 März 2025

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 Bacillus subtilis and other Gram-positive bacteria, including the pathogens Staphylococcus aureus and Mycobacterium tuberculosis. 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 B. subtilis toward metabolic dormancy during spore formation. A knockout of mdfA stimulates gene expression in the developing spore, while aberrant expression of mdfA 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 mdfA. Finally, a cocrystal structure reveals that MdfA binds to the ClpC N-terminal domain at a location analogous to that on the M. tuberculosis 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.

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Zitieren

MdfA is a novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore. / Massoni, Shawn C.; Evans, Nicola J.; Hantke, Ingo et al.
in: Genes and Development, Jahrgang 39, Nr. 7, 14.03.2025, S. 510-523.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Massoni, SC, Evans, NJ, Hantke, I, Fenton, C, Torpey, JH, Collins, KM, Krysztofinska, EM, Muench, JH, Thapaliya, A, Martínez-Lumbreras, S, Ferrell, SH, Slater, C, Wang, X, Fekade, R, Obwar, S, Yin, S, Vazquez, A, Prior, CB, Turgay, K, Isaacson, RL & Camp, AH 2025, 'MdfA is a novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore', Genes and Development, Jg. 39, Nr. 7, S. 510-523. https://doi.org/10.1101/gad.352498.124
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., Ferrell, S. H., Slater, C., Wang, X., Fekade, R., Obwar, S., Yin, S., Vazquez, A., Prior, C. B., Turgay, K., ... Camp, A. H. (2025). MdfA is a novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore. Genes and Development, 39(7), 510-523. https://doi.org/10.1101/gad.352498.124
Massoni SC, Evans NJ, Hantke I, Fenton C, Torpey JH, Collins KM et al. MdfA is a novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore. Genes and Development. 2025 Mär 14;39(7):510-523. doi: 10.1101/gad.352498.124
Massoni, Shawn C. ; Evans, Nicola J. ; Hantke, Ingo et al. / MdfA is a novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore. in: Genes and Development. 2025 ; Jahrgang 39, Nr. 7. S. 510-523.
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title = "MdfA is a novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore",
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 Bacillus subtilis and other Gram-positive bacteria, including the pathogens Staphylococcus aureus and Mycobacterium tuberculosis. 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 B. subtilis toward metabolic dormancy during spore formation. A knockout of mdfA stimulates gene expression in the developing spore, while aberrant expression of mdfA 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 mdfA. Finally, a cocrystal structure reveals that MdfA binds to the ClpC N-terminal domain at a location analogous to that on the M. tuberculosis 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.",
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TY - JOUR

T1 - MdfA is a novel ClpC adaptor protein that functions in the developing Bacillus subtilis spore

AU - Massoni, Shawn C.

AU - Evans, Nicola J.

AU - Hantke, Ingo

AU - Fenton, Colleen

AU - Torpey, James H.

AU - Collins, Katherine M.

AU - Krysztofinska, Ewelina M.

AU - Muench, Janina H.

AU - Thapaliya, Arjun

AU - Martínez-Lumbreras, Santiago

AU - Ferrell, Sé Hart

AU - Slater, Celia

AU - Wang, Xinyue

AU - Fekade, Ruth

AU - Obwar, Sandra

AU - Yin, Siyu

AU - Vazquez, Alishba

AU - Prior, Christopher B.

AU - Turgay, Kürsa

AU - Isaacson, Rivka L.

AU - Camp, Amy H.

N1 - Publisher Copyright: © 2025 Massoni et al.

PY - 2025/3/14

Y1 - 2025/3/14

N2 - 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 Bacillus subtilis and other Gram-positive bacteria, including the pathogens Staphylococcus aureus and Mycobacterium tuberculosis. 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 B. subtilis toward metabolic dormancy during spore formation. A knockout of mdfA stimulates gene expression in the developing spore, while aberrant expression of mdfA 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 mdfA. Finally, a cocrystal structure reveals that MdfA binds to the ClpC N-terminal domain at a location analogous to that on the M. tuberculosis 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.

AB - 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 Bacillus subtilis and other Gram-positive bacteria, including the pathogens Staphylococcus aureus and Mycobacterium tuberculosis. 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 B. subtilis toward metabolic dormancy during spore formation. A knockout of mdfA stimulates gene expression in the developing spore, while aberrant expression of mdfA 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 mdfA. Finally, a cocrystal structure reveals that MdfA binds to the ClpC N-terminal domain at a location analogous to that on the M. tuberculosis 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.

KW - AAA proteases

KW - adaptor

KW - Bacillus subtilis

KW - ClpC

KW - ClpCP

KW - MdfA

KW - protein degradation

KW - sporulation

KW - X-ray crystallography

KW - YjbA

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U2 - 10.1101/gad.352498.124

DO - 10.1101/gad.352498.124

M3 - Article

C2 - 40086879

AN - SCOPUS:105003061515

VL - 39

SP - 510

EP - 523

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 7

ER -