Mechanistic insights into JSS1_004-mediated antagonism of the DndBCDE-FGH restriction system and engineering applications.

ABSTRACT: The bacterial DNA phosphorothioate (PT) modification system is orchestrated by the DndCDE enzymatic complex. This system collaborates with restriction components DndF, DndG, and DndH to establish a widespread prokaryotic anti-phage defense network. In the evolutionary arms race, phages such as JSS1 have evolved counter strategies, including the expression of the JSS1_004 protein, to subvert PT-mediated host immunity. Although the N-terminal kinase domain of JSS1_004 is known to inhibit DndFGH through phosphorylation-dependent inactivation, the functional role of its C-terminal shutoff domain remained enigmatic. Here, we demonstrate that both domains are indispensable for full antagonistic activity against the DndBCDE-FGH system. Genetic dissection revealed that the absence of either domain

SUBMITTER: He Y 

PROVIDER: S-EPMC12345140 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature