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Periplasmic protein quality control at atomic level in live cells

Author

Listed:
  • Lisandro J. González

    (National University of Rosario (IBR-CONICET-UNR)
    National University of Rosario (UNR))

  • Francisco J. Hita

    (National University of Rosario (IBR-CONICET-UNR))

  • Letizia Pontoriero

    (University of Florence)

  • Roberta Pierattelli

    (University of Florence)

  • Andres Binolfi

    (National University of Rosario (IBR-CONICET-UNR)
    Argentinian Platform of Structural Biology and Metabolomics (PLABEM))

  • Alejandro J. Vila

    (National University of Rosario (IBR-CONICET-UNR)
    National University of Rosario (UNR)
    Argentinian Platform of Structural Biology and Metabolomics (PLABEM))

Abstract

The periplasm of gram-negative bacteria facilitates critical functions, including nutrient uptake, cell wall metabolism, antibiotic resistance, and virulence. Efficient quality control of proteins involved in these processes is crucial for bacterial fitness and survival. The limited size of the periplasm has hindered high-resolution mechanistic investigations of complex processes within this compartment. Using in-cell NMR spectroscopy, we dissect the mechanism of periplasmic quality control of the metallo-β-lactamase NDM-1 under conditions of zinc starvation, which destabilizes its native structure promoting its degradation. We show that the protease Prc targets membrane-bound NDM-1 at specific residues and secondary structure motifs, while DegP processes peptides generated by Prc. This approach discloses the concerted mechanism of these proteases at atomic resolution in the periplasm of live cells.

Suggested Citation

  • Lisandro J. González & Francisco J. Hita & Letizia Pontoriero & Roberta Pierattelli & Andres Binolfi & Alejandro J. Vila, 2025. "Periplasmic protein quality control at atomic level in live cells," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62340-6
    DOI: 10.1038/s41467-025-62340-6
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