9JFL

Molecular basis of the phosphorothioation-sensing antiphage defence system DndBCDE-DndI

Summary for 9JFL

• Entry DOI: 10.2210/pdb9jfl/pdb
• Descriptor: DUF262 domain-containing protein, TRIETHYLENE GLYCOL, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: bacterial defense system, dna nuclease enzyme, ntpase, dna binding protein
• Biological source: Salmonella enterica
• Total number of polymer chains: 2
• Total formula weight: 140355.71

Authors

Dan, W. (deposition date: 2024-09-04, release date: 2024-12-11, Last modification date: 2025-01-01)

Primary citation

Tang, Y.,Wu, D.,Zhang, Y.,Liu, X.,Chu, H.,Tan, Q.,Jiang, L.,Chen, S.,Wu, G.,Wang, L.
Molecular basis of the phosphorothioation-sensing antiphage defense system IscS-DndBCDE-DndI.
Nucleic Acids Res., 52:13594-13604, 2024

PubMed Abstract: Phosphorothioation serves as a DNA backbone modification mechanism, wherein a sulfur atom substitutes the nonbridging oxygen atom within the phosphodiester, facilitated by the gene products of dndABCDE or sspABCD. The combination of dndABCDE with dndFGH forms a bona fide defense system, where the DndFGH protein complex exhibits DNA nickase and DNA translocase activities to prevent phage invasion. In this study, we identified that dndI, co-transcribed with dndFGH, can independently couple with iscS-dndBCDE as an anti-phage defense system. Moreover, we resolved the crystal structure of DndI from Salmonella at a resolution of 3.10 Å. We discovered that its residue Y25, residing within a hydrophobic region of DndI, is involved in phosphorothioate (PT) sensing. Upon sensing PT modifications at 5'-GPSAAC-3'/5'-GPSTTC-3', the ATPase activity of DndI is stimulated, which subsequently triggers a conformational transition, facilitating the dissociation of DndI from self-DNA, thereby allowing DndI to avoid cleaving self-DNA while restricting PT-deficient phage DNA. This research broadens the knowledge of the mechanistic diversity underlying PT-based defense systems and highlights their complexity in the course of evolution.

PubMed: 39611571
DOI: 10.1093/nar/gkae1133

Experimental method

X-RAY DIFFRACTION (3 Å)