9L5U

Papain-like cysteine protease toxin/immunity pair

Summary for 9L5U

• Entry DOI: 10.2210/pdb9l5u/pdb
• Descriptor: DUF4150 domain-containing protein, Cpi1 (3 entities in total)
• Functional Keywords: papain-like cysteine protease, toxin/immunity pair, toxin
• Biological source: Escherichia coli DSM 30083 = JCM 1649 = ATCC 11775; More
• Total number of polymer chains: 4
• Total formula weight: 56111.73

Authors

Chen, P.-P.,Hsia, K.-C.,Ting, S.-Y.,Chen, Y.-C. (deposition date: 2024-12-23, release date: 2025-06-04)

Primary citation

Song, P.Y.,Tsai, C.E.,Chen, Y.C.,Huang, Y.W.,Chen, P.P.,Wang, T.H.,Hu, C.Y.,Chen, P.Y.,Ku, C.,Hsia, K.C.,Ting, S.Y.
An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE.
Plos Biol., 23:e3003208-e3003208, 2025

PubMed Abstract: Bacteria deploy a diverse arsenal of toxic effectors to antagonize competitors, profoundly influencing the composition of microbial communities. Previous studies have identified an interbacterial toxin predicted to exhibit proteolytic activity that is broadly distributed among gram-negative bacteria. However, the precise mechanism of intoxication remains unresolved. Here, we demonstrate that one such protease toxin from Escherichia coli, Cpe1, disrupts DNA replication and chromosome segregation by cleaving conserved sequences within the ATPase domain of type II DNA topoisomerases GyrB and ParE. This cleavage effectively inhibits topoisomerase-mediated relaxation of supercoiled DNA, resulting in impaired bacterial growth. Cpe1 belongs to the papain-like cysteine protease family and is associated with toxin delivery pathways, including the type VI secretion system and contact-dependent growth inhibition. The structure of Cpe1 in complex with its immunity protein reveals a neutralization mechanism involving competitive substrate binding rather than active site occlusion, distinguishing it from previously characterized effector-immunity pairs. Our findings unveil a unique mode of interbacterial intoxication and provide insights into how bacteria protect themselves from self-poisoning by protease toxins.

PubMed: 40424468
DOI: 10.1371/journal.pbio.3003208

Experimental method

X-RAY DIFFRACTION (1.87 Å)