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TitleMolecular basis of bacterial DSR2 anti-phage defense and viral immune evasion.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 3954, Year 2024
Publish dateMay 10, 2024
AuthorsJiafeng Huang / Keli Zhu / Yina Gao / Feng Ye / Zhaolong Li / Yao Ge / Songqing Liu / Jing Yang / Ang Gao /
PubMed AbstractDefense-associated sirtuin 2 (DSR2) systems are widely distributed across prokaryotic genomes, providing robust protection against phage infection. DSR2 recognizes phage tail tube proteins and ...Defense-associated sirtuin 2 (DSR2) systems are widely distributed across prokaryotic genomes, providing robust protection against phage infection. DSR2 recognizes phage tail tube proteins and induces abortive infection by depleting intracellular NAD, a process that is counteracted by another phage-encoded protein, DSR Anti Defense 1 (DSAD1). Here, we present cryo-EM structures of Bacillus subtilis DSR2 in its apo, Tube-bound, and DSAD1-bound states. DSR2 assembles into an elongated tetramer, with four NADase catalytic modules clustered in the center and the regulatory-sensing modules distributed at four distal corners. Interestingly, monomeric Tube protein, rather than its oligomeric states, docks at each corner of the DSR2 tetramer to form a 4:4 DSR2-Tube assembly, which is essential for DSR2 NADase activity. DSAD1 competes with Tube for binding to DSR2 by occupying an overlapping region, thereby inhibiting DSR2 immunity. Thus, our results provide important insights into the assembly, activation and inhibition of the DSR2 anti-phage defense system.
External linksNat Commun / PubMed:38729958 / PubMed Central
MethodsEM (single particle)
Resolution3.58 - 4.15 Å
Structure data

37606

8wks

EMDB-37606, PDB-8wks:
Cryo-EM structure of DSR2-TUBE complex
Method: EM (single particle) / Resolution: 3.58 Å

37607

8wkt

EMDB-37607, PDB-8wkt:
Cryo-EM structure of DSR2-DSAD1 complex
Method: EM (single particle) / Resolution: 3.86 Å

37610

8wkx

EMDB-37610, PDB-8wkx:
Cryo-EM structure of DSR2
Method: EM (single particle) / Resolution: 4.15 Å

Source
  • bacillus subtilis subsp. natto (strain best195) (bacteria)
  • siphoviridae sp. ct0106 (virus)
  • caudoviricetes (bacterial and archaeal viruses with head-tail morphology)
KeywordsSTRUCTURAL PROTEIN / Anti-phage immune / NADase / Defense-associated sirtuin 2 / DSR2 / Phage tail tube protein / DSR Anti Defense 1 / DSAD1 / Bacteria-phage interaction / SURFACTANT PROTEIN

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