8XCL

Character of TseP: a dual functional effector of type VI secretion system

8XCL の概要

• エントリーDOI: 10.2210/pdb8xcl/pdb
• 分子名称: EF-hand domain-containing protein (2 entities in total)
• 機能のキーワード: t6ss, interspecies interaction, bifunctional effector, peptidoglycan hydrolysis, hydrolase
• 由来する生物種: Aeromonas dhakensis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27257.65

構造登録者

Qin, W.M.,Zhao, T.,Dong, T.,Wang, Z.H. (登録日: 2023-12-09, 公開日: 2025-04-23)

主引用文献

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

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: 40063082
DOI: 10.7554/eLife.101125

実験手法

X-RAY DIFFRACTION (2.27 Å)