Targeted Protein Degradation in E. coli

Targeted Protein Degradation in Escherichia coli using CLIPPERs.

Izert-Nowakowska MA, Klimecka MM, Antosiewicz A, Wróblewski K, Kowalski JJ, Bandyra KJ, Góral TK, Kmiecik S, Serwa RA, Górna MW.

EMBO Reports (2025), DOI: 10.1038/s44319-025-00510-9

We demonstrated that the induced degradation of an unmodified, degronless target is possible in Escherichia coli - this was achieved by the direct recruitment of the ClpXP protease. CLIPPERs are new peptide tools for targeted protein degradation in bacteria.

• CLIPPER peptides containing the SspB-derived XB motif can bind and recruit the ClpXP protease
• GroTACs, which are CLIPPERs targeting the essential chaperone GroEL, show an antimicrobial effect in Escherichia coli
• GroTACs induce progressive GroEL degradation over time, leading to extensive proteome rewiring in accordance with the GroEL function as a major chaperone