Cryo-EM structure of the GroEL-GroTAC complex helps unravelling a new method for degrading bacterial proteins
06 07 2025
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New, universal tools for targeted protein degradation in bacteria can help to accelerate protein function studies and antimicrobial research. A team of scientists fom the University of Warsaw led by Maria Górna from the Faculty of Chemistry described a new method for degrading bacterial proteins using plasmid-encoded degrader peptides which deliver target proteins for degradation by a highly conserved ClpXP protease. They demonstrated the mode of action of the degraders on a challenging essential target, GroEL. The studies in bacteria were complemented by in vitro binding and structural studies. They showed that the expression of degrader peptides resulted in a temperature-dependent growth inhibition and depletion of GroEL levels over time. The reduction of GroEL levels was accompanied by dramatic proteome alterations. The presented method offers a new alternative approach for regulating protein levels in bacteria without genomic modifications or tag fusions. Our studies demonstrate that ClpXP is an attractive protease for the future use in bacterial-targeted protein degradation. Their finding have been pusblished in the EMBO reports journal.
The complex of GroEL with chemically synthesised GroTAC3 peptide was imaged with a Glacios electron microscop that operated at 200 kV and was equipped with a Falcon 3EC camera at the Cryomicroscopy and Electron Diffraction Core Facility at the Centre of New Technologies, University of Warsaw with the help of Tomasz Góral.
Read more: Izert-Nowakowska, Matylda Anna; Klimecka, Maria Magdalena; Antosiewicz, Anna; Wróblewski, Karol; Kowalski, Jakub Józef; Bandyra, Katarzyna Justyna; Góral, Tomasz; Kmiecik, Sebastian; Serwa, Remigiusz Adam and Górna, Maria Wiktoria, “Targeted protein degradation in Escherichia coli using CLIPPERs”, EMBO reports. https://doi.org/10.1038/s44319-025-00510-9