Periplasmic protein quality control at atomic level in live cells
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.
Authors
- Francisco J. Hita (ORCID: https://orcid.org/0000-0003-3576-3342)
- Letizia Pontoriero (ORCID: https://orcid.org/0000-0002-5586-1305)
- Roberta Pierattelli (ORCID: https://orcid.org/0000-0001-7755-0885)
- Lisandro J. González (ORCID: https://orcid.org/0000-0002-0575-1810)
- Alejandro J. Vila (ORCID: https://orcid.org/0000-0002-7978-3233)
- Andrés Binolfi (ORCID: https://orcid.org/0000-0003-2374-0864)
Institutions
- National University of Rosario (AR)
- Centro Científico Tecnólogico - Rosario (AR)
- Interuniversity Consortium for Magnetic Resonance (IT)
- Instituto Cardiovascular de Rosario (AR)
- Instituto de Biología Molecular y Celular de Rosario (AR)
- University of Florence (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-24
- DOI
- https://doi.org/10.1038/s41467-025-62340-6
- Citations
- 3
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 1.77
Funders
- Richard Lounsbery Foundation
- European Commission
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Ministerio de Ciencia, Tecnología e Innovación Productiva
- Ministero della Salute
- Ministero degli Affari Esteri e della Cooperazione Internazionale
- Agencia Santafesina de Ciencia, Tecnología e Innovación