8XCL
Character of TseP: a dual functional effector of type VI secretion system
Summary for 8XCL
| Entry DOI | 10.2210/pdb8xcl/pdb |
| Descriptor | EF-hand domain-containing protein (2 entities in total) |
| Functional Keywords | t6ss, interspecies interaction, bifunctional effector, peptidoglycan hydrolysis, hydrolase |
| Biological source | Aeromonas dhakensis |
| Total number of polymer chains | 1 |
| Total formula weight | 27257.65 |
| Authors | |
| Primary citation | Wang, Z.H.,An, Y.,Zhao, T.,Pei, T.T.,Wang, D.Y.,Liang, X.,Qin, W.,Dong, T. Amidase and lysozyme dual functions in TseP reveal a new family of chimeric effectors in the type VI secretion system. Elife, 13:-, 2025 Cited by PubMed Abstract: Peptidoglycan (PG) serves as an essential target for antimicrobial development. An overlooked reservoir of antimicrobials lies in the form of PG-hydrolyzing enzymes naturally produced for polymicrobial competition, particularly those associated with the type VI secretion system (T6SS). Here, we report that a T6SS effector TseP, from , represents a family of effectors with dual amidase-lysozyme activities. In vitro PG-digestion coupled with LC-MS analysis revealed the N-domain's amidase activity, which is neutralized by either catalytic mutations or the presence of the immunity protein TsiP. The N-domain, but not the C-domain, of TseP is sufficient to restore T6SS secretion in T6SS-defective mutants, underscoring its critical structural role. Using pull-down and secretion assays, we showed that these two domains interact directly with a carrier protein VgrG2 and can be secreted separately. Homologs in and exhibited analogous dual functions. Additionally, N- and C-domains display distinctive GC contents, suggesting an evolutionary fusion event. By altering the surface charge through structural-guided design, we engineered the TseP effector that successfully lyses otherwise resistant cells, enabling the T6SS to inhibit in a contact-independent manner. This research uncovers TseP as a new family of bifunctional chimeric effectors targeting PG, offering a potential strategy to harness these proteins in the fight against antimicrobial resistance. PubMed: 40063082DOI: 10.7554/eLife.101125 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.27 Å) |
Structure validation
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